The central challenge the team confronted is one that has long frustrated microbiome researchers. When an antibiotic treatment changes both the composition of the gut microbiota and the expression of host genes, it is extraordinarily difficult to determine which host changes are caused by the microbial shifts and which are caused by the drug acting directly on host cells. Germ-free animals can reveal whether a perturbation acts directly on the host, but until now there was no rigorous statistical tool that could predict, from observational data in conventional animals, whether a given host response was microbiota dependent or microbiota independent. The researchers set out to close that gap.

Their experimental design was ambitious. They treated specific pathogen-free mice with four commonly used antibiotics—vancomycin, ampicillin, metronidazole and neomycin—either individually or in combination, and delivered them through three different routes: oral gavage, intraperitoneal injection and intravenous injection. Mice were treated twice daily for three and a half days, mimicking the shorter antibiotic regimens now favoured in clinical practice. Stool samples were collected before and after treatment to profile the microbiota using 16S rRNA amplicon sequencing, while colonic tissue was harvested for RNA sequencing to capture the host transcriptional response.

One of the most surprising findings concerned vancomycin itself. This is a large, hydrophilic molecule that should cross the gut mucosa poorly, which is precisely why it is given orally to treat intestinal infections like Clostridioides difficile. Yet when the researchers administered vancomycin systemically by intraperitoneal injection, mass spectrometry confirmed that detectable amounts of the drug reached the small intestinal and colonic lumen. The consequences for the microbiota were distinct depending on the route: oral administration drove a dramatic increase in Enterobacteriaceae, while systemic treatment increased Tannerellaceae. Both are Gram-negative families, but the fact that systemic vancomycin reshapes the gut community at all overturns a long-standing assumption about the drug’s pharmacokinetics.

When the team turned to the host transcriptome, the picture became even more interesting. Intraperitoneal vancomycin affected the largest number of colonic transcripts of any antibiotic studied, and gene set enrichment analysis revealed that the affected pathways included antigen presentation via major histocompatibility complex class II molecules—a core immune function of the gut epithelium. A random forest classifier trained on the transcriptional data could distinguish each antibiotic and each administration route with high accuracy, confirming that different antibiotics produce unique host transcriptional signatures. Remarkably, when the four antibiotics were combined, many of the individual effects on core clock genes were suppressed, and even clinically relevant pairs such as vancomycin plus metronidazole produced non-additive effects on the host that could not be predicted from the single-drug responses.

To disentangle microbiota-dependent from microbiota-independent effects, the researchers developed CompoRes, a computational tool that integrates microbial compositional data with host gene expression profiles. The algorithm first infers correlations among microbial taxa using SPARCC, a method designed for compositional data, and hierarchically clusters them into operational compositional units. It then computes log-ratios of all possible pairs of these units and correlates them with gene expression. Because the number of comparisons is vast relative to sample size, the tool generates a null distribution by shuffling the data at least fifty times, yielding a rigorous P value for each gene. The approach was validated on synthetic data and on experimental ground truths: germ-free mice treated with intraperitoneal vancomycin, where the drug can only act directly on the host, and germ-free mice receiving a faecal microbiota transplant from orally treated mice, where the effect can only flow through the microbiota.

Applying CompoRes to the clock genes Ciart, Nfil3, Per3 and Dbp revealed a striking route-dependent dichotomy. In mice treated orally with vancomycin, the expression of these core circadian regulators correlated strongly with changes in microbiota composition, consistent with previous work showing that the gut microbiota oscillates in a circadian pattern and programs host transcriptome oscillations. But in mice receiving the same drug systemically, the same genes showed no correlation with the microbiota whatsoever. The tool had predicted, purely from data in conventional animals, that systemic vancomycin disrupts circadian gene expression in the gut through a direct, non-microbial pathway. Subsequent experiments in germ-free mice confirmed this prediction: intraperitoneal vancomycin altered core clock gene expression across a 24-hour cycle in animals that had no microbes at all.

The physiological consequences of this microbiota-independent disruption proved to be behavioural. In germ-free mice, vancomycin reversed the normal diurnal expression pattern of metabolic genes such as Ppara, Cd36, Lpl and Fabp4, which typically peak during the light phase when nocturnal mice are fasting. The team found that vancomycin reduced food intake in both germ-free and conventional mice, with feeding normalising after treatment ceased. Transcriptional analysis showed that the drug uniquely altered enteric nervous system transcripts, and immunofluorescence imaging revealed that fluorescein-labelled vancomycin was internalised into myenteric plexus neurons following systemic injection but not oral administration. The drug induced expression of the neuropeptide neuromedin U and its receptor NMUR2, and mice lacking neuromedin U were resistant to vancomycin-induced hypophagia, pinpointing the molecular mechanism by which the antibiotic suppresses appetite.

The downstream immune consequences were equally profound. Expression of the MHC class II genes H2-Aa and H2-Ab1 in the colonic epithelium normally peaks at a specific circadian time point, and the researchers discovered that this oscillation persists in germ-free mice—unlike in the small intestine, where microbial presence is required. They further showed that glucose directly induces H2-Ab1 expression in fasting germ-free mice and in intestinal epithelial cells in vitro, indicating that colonic MHC class II expression follows a diurnal, glucose-responsive pattern dictated by feeding. Vancomycin-induced hypophagia suppressed this peak entirely, meaning the antibiotic disrupts a key antigen-presentation rhythm in the gut through a direct behavioural pathway rather than through any change to the microbiota.

Perhaps most remarkably, the molecular response to vancomycin proved to be evolutionarily conserved. When the researchers reared Drosophila melanogaster on vancomycin-laced food and sequenced adult fly brain RNA, they found that the fly homologues of the mammalian Clock gene and its downstream target timeless were altered, as was klumpfuss, a gene controlling feeding behaviour in flies. The fly orthologue of the NMU receptor was induced in response to the drug, mirroring what the team had observed in mice. This preservation of the vancomycin response across evolutionarily distant organisms suggests that the antibiotic taps into an ancient cellular stress pathway, one that links metabolism, circadian biology and immunity through mechanisms that operate independently of any microbe. The work challenges the microbiota-only model of antibiotic action and provides a framework for identifying direct effects of environmental perturbations on host physiology, with implications for understanding how antibiotics shape immunity, metabolism and circadian health in clinical practice and beyond.

Subject of Research: Microbiology

Article Title: Disentangling microbiota-dependent and -independent impacts of antibiotics on host physiology

Article References: Zelik, L., Levin, Y., Sawaed, J., Telpaz, S., Zigdon, M., Nuriel-Ohayon, M., Rubin, E., Gordon, A., Mogilevski, Z., Yehuda, A., Awad, A., Shaalan, H., Ben-Simon, S., Modilevsky, S., Naama, M., Dalvi, J., Moadi, L., Kurtz, M., Perez, S., … Bel, S. (2026). Disentangling microbiota-dependent and -independent impacts of antibiotics on host physiology. Nature Microbiology. https://doi.org/10.1038/s41564-026-02453-w

Image Credits: AI Generated

DOI: 10.1038/s41564-026-02453-w

Keywords: antibiotics, gut microbiota, circadian rhythms, vancomycin, MHC class II, neuromedin U, germ-free mice, CompoRes, host physiology, microbiome, Disentangling, microbiota-dependent

Omadacycline belongs to the aminomethylcycline subclass, the latest generation of tetracycline derivatives, engineered to overcome the two major resistance mechanisms that disable older tetracyclines: efflux pumps that expel the drug from bacterial cells and ribosomal protection proteins that shield the drug’s binding site. Because of these modifications, omadacycline retains activity against methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, and many gram-negative pathogens, which is precisely why clinicians have been eager to see it deployed against difficult infections. Until now, however, its approved indications covered adults with community-acquired bacterial pneumonia and acute bacterial skin infections, leaving pediatric use essentially uncharted territory.

The research team, led by pharmacists at the First Affiliated Hospital of Nanchang University in Jiangxi, China, combed electronic medical records for patients aged 8 to 17 who received omadacycline for infectious diseases. The retrospective design means the drug was given at the discretion of treating physicians in real clinical practice, not under the controlled conditions of a randomized trial. Clinical effectiveness was assessed on the day before discharge and graded on a four-point scale: cured, markedly effective, improved, or ineffective. Effective outcomes were defined as complete resolution or significant improvement of infection-related symptoms and signs without the need for additional antimicrobial therapy.

The headline result was striking. Of the 267 patients, 20, or 7.5 percent, were cured, 109, or 40.8 percent, were markedly effective, and 115, or 43.1 percent, were improved, adding up to a clinical effective rate of 91.4 percent. Only 23 patients, or 8.6 percent, failed to respond. In other words, roughly nine out of ten children and adolescents treated with omadacycline left the hospital with their infections resolved or substantially improved, without needing rescue antibiotics. For a drug never before documented in this age group, the aggregate outcome pattern closely mirrors what adult trials and real-world adult series have reported.

Statistical analysis revealed which factors tipped the balance toward success. Patients with pulmonary infection were significantly more likely to achieve effective outcomes than those with infections at other sites, with the difference reaching statistical significance at P equal to 0.012. A longer duration of combination therapy, in which omadacycline was given alongside other antibiotics, was also associated with a greater probability of effectiveness, at P equal to 0.030. The authors suggest that the drug’s strong lung penetration, a hallmark of the aminomethylcyclines, may partly explain the pulmonary advantage, while combination regimens may have provided broader initial coverage in severely ill children until pathogens were identified.

One of the most clinically useful findings concerned fever. Body temperature declined continuously after the medication was started, a trend that was highly significant across the treatment period at P less than 0.001. When the researchers compared the effective group with the ineffective group, the children who ultimately responded had significantly lower body temperatures on day 3, at P equal to 0.035, and day 4, at P equal to 0.002, after the medication began. This defervescence pattern could eventually serve as an early bedside signal, allowing clinicians to distinguish responders from non-responders within the first few days of therapy and adjust treatment before the infection gains further ground.

Safety was the other half of the equation, and here the short-term picture was reassuring. Only 5 patients developed mild liver injury after receiving the drug, and no moderate or severe liver injury was recorded anywhere in the cohort. Laboratory indices from routine blood examinations, including white blood cells, neutrophils, lymphocytes, and platelets, as well as liver function markers such as alanine transaminase, aspartate aminotransferase, total bilirubin, and direct bilirubin, and renal function measures including uric acid, all remained within normal ranges before and after treatment, and the observed changes lacked clinical significance. For a tetracycline-class drug, a class historically associated with photosensitivity, tooth discoloration, and gastrointestinal upset in children, this laboratory profile is a notable point in the drug’s favor.

The study was conducted in accordance with the Declaration of Helsinki, approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University, and carried out with a waiver of informed consent given its retrospective design. Funding came from the National Natural Science Foundation of China and the Natural Science Foundation of Jiangxi Province. The authors declared no competing interests, and the article is published open access under a Creative Commons license, making the full dataset description and supplementary materials freely available to clinicians and researchers worldwide.

Yet the authors are careful about what these results can and cannot prove. A retrospective cohort cannot eliminate selection bias, since physicians chose omadacycline for particular patients for particular reasons, and the absence of a control group means the outcomes cannot be attributed to the drug with certainty. The pediatric population studied was also limited to children aged 8 and above, leaving younger children entirely unstudied. The authors explicitly state that prospective controlled studies are needed to confirm the findings before omadacycline can be considered an evidence-based option for pediatric infections.

Even with those caveats, the study marks a meaningful step in pediatric antimicrobial therapy. As multidrug-resistant bacteria continue to erode the utility of older antibiotics, every new agent that can be safely extended to children expands the therapeutic arsenal for the most vulnerable patients. If prospective trials bear out the 91.4 percent effective rate and the clean short-term safety profile reported here, omadacycline could become a valuable option for children with pneumonia caused by resistant pathogens, and the defervescence signature identified in this cohort may give clinicians an early, practical tool for judging whether the drug is working. For now, the message is one of cautious optimism: the newest tetracycline has taken its first documented steps in pediatric medicine, and the early results look promising.

Subject of Research: Infectious Diseases

Article Title: Omadacycline in pediatric patients with predominantly pulmonary infections: a retrospective, real-world study

Article References: Liu, J., Liu, J., Zhang, Z., Huang, J., Liu, J., & Ouyang, A. (2026). Omadacycline in pediatric patients with predominantly pulmonary infections: a retrospective, real-world study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14317-z

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14317-z

Keywords: omadacycline, tetracycline, pediatrics, pulmonary infection, antibiotics, antimicrobial resistance, BMC Infectious Diseases, pediatric, patients, predominantly, pulmonary, infections

The material at the heart of the study belongs to a well-known family of compounds with the general formula AB2O4, known as spinels. These mixed metal oxides are stable semiconductors that have repeatedly demonstrated strong photocatalytic efficiency in destroying organic pollutants. In a photocatalytic process, the semiconductor absorbs photons, generating reactive species such as hydroxyl radicals and superoxide radicals that attack pollutant molecules and tear them apart. How well an oxide performs this job depends on several parameters, including its band gap energy, crystallinity, specific surface area and morphology. The Moroccan team set out to tune those parameters by replacing half of the zinc ions in zinc aluminate with magnesium, producing a compound written as Mg0.5Zn0.5Al2O4, and then testing it against tetracycline hydrochloride, a widely used antibiotic chosen as a representative pharmaceutical pollutant.

The preparation method is one of the most appealing aspects of the work, because it is deliberately simple and inexpensive. The researchers dissolved analytical grade zinc nitrate, aluminium nitrate and magnesium nitrate in water at a metal ion concentration of 0.2 molar, keeping the stoichiometric molar ratio of trivalent to divalent cations at 0.5. Urea was added in excess to act simultaneously as a chelating agent and as a fuel. The solution was evaporated at 80 degrees Celsius until a viscous gel formed, then dried at 120 degrees Celsius for 24 hours to yield a xerogel. That xerogel was pre-calcined at 300 degrees Celsius for 12 hours in air to burn off the organic matter through pyrolysis, and the resulting precursor was finally heat-treated at 700 degrees Celsius for 5 hours. This soft chemistry route avoids the high temperatures and elaborate equipment often required to make high-quality spinel ceramics.

Characterisation of the powders followed established analytical protocols. Thermogravimetry and differential thermal analysis tracked the crystallisation of the xerogel, revealing a total mass loss of about 78 percent between 30 and 550 degrees Celsius. Those mass losses appeared as thermal effects attributable to dehydration, the elimination of ammonium nitrate species, decomposition of the complexing agent and the eventual crystallisation of the oxide phase. X-ray diffraction, performed with a Bruker D8 Advance diffractometer using copper K-alpha radiation, then mapped the crystalline structure of samples taken before and after the high-temperature treatment. The pre-calcined sample showed broad, weak diffraction peaks signalling the very beginning of crystallisation, while the sample annealed at 700 degrees Celsius displayed sharper, more intense reflections, a clear sign of improved crystallinity.

The diffraction pattern of the annealed powder told a satisfying story. Peaks appeared at 2-theta values of 31.2, 36.8, 44.8, 49.1, 55.8, 59.4, 65.3, 74.1 and 77.5 degrees, and these could be indexed to the (220), (311), (400), (331), (422), (511), (440), (620) and (533) crystallographic planes of a cubic spinel structure belonging to the Fd-3m space group. Crucially, no additional diffraction peaks were detected, indicating that a single-phase spinel had formed rather than a mixture of unwanted secondary phases. Scanning electron microscopy with a JEOL JSM-6400 instrument showed that the calcined powder consists of submicron-sized agglomerates, a morphology typical of powders produced by gel-based combustion and chelation routes. The authors note that the study was limited to a single magnesium-to-zinc ratio of x equal to 0.5, and that a systematic survey of different ratios would be needed to fully map how composition controls phase formation, crystallinity, optical behaviour and catalytic performance.

Optical measurements provided the key numbers that connect the material to its photocatalytic role. Ultraviolet-visible absorption spectroscopy revealed a broad absorption band extending into the visible region. Using Tauc analysis, in which the absorption coefficient raised to an exponent appropriate for direct transitions is plotted against photon energy, the team identified two quasi-linear regions corresponding to apparent transition energies of approximately 3.14 and 4.65 electronvolts. The authors are careful to point out that these values should not necessarily be read as two independent fundamental band gaps. The lower energy of 3.14 electronvolts is treated as the more relevant optical absorption edge for discussing photocatalytic behaviour under ultraviolet irradiation, while the higher-energy feature is regarded as an apparent transition whose precise origin cannot be pinned down from the available diffraction and spectroscopy data alone.

With the catalyst characterised, the team turned to the practical test: degrading tetracycline hydrochloride in water. The experiments took place in a cylindrical reactor built around a 250-millilitre double-walled Pyrex beaker held at room temperature. The light source combined two UVA lamps and two UVB lamps, each rated at 10 watts and positioned roughly 12 centimetres from the beaker, plus a 15-watt submersible UVC lamp placed directly in the reaction solution. The whole apparatus sat inside an opaque box to exclude ambient sunlight, and no optical filters were used. The pollutant solution started at a concentration of 30 milligrams per litre, and its absorbance maximum at 357 nanometres allowed concentration to be tracked with a linear calibration curve obeying the Beer-Lambert law.

The results unfolded in two stages. First, 50 milligrams of the Mg0.5Zn0.5Al2O4 powder were dispersed in 200 millilitres of the antibiotic solution and stirred in the dark. Adsorption-desorption equilibrium was reached within 30 minutes, during which 17 percent of the tetracycline disappeared from solution, an initial removal attributed mainly to adsorption onto the catalyst surface. Then the lamps were switched on. Samples collected every 30 minutes showed a steady decline in absorbance, and by the end of two hours of ultraviolet irradiation a total of 76 percent of the pollutant had been eliminated. The removal process followed pseudo-first-order kinetics, with an apparent rate constant of 0.020 per minute. As a benchmark, the authors cite a recent study reporting 66.9 percent tetracycline degradation with the spinel ZnFe2O4 alone, although they caution that differences in catalyst composition, pollutant concentration, catalyst dosage and irradiation conditions make direct comparisons between spinel materials imperfect.

The authors are equally candid about what the experiments cannot yet prove. Because no light-only photolysis control and no radical-scavenger tests were performed, the specific contributions of direct photolysis and of reactive oxygen species such as hydroxyl and superoxide radicals cannot be experimentally separated; their involvement is discussed only on the basis of the generally accepted photocatalytic mechanism. The team also notes that further control experiments using undoped ZnAl2O4 would be needed to quantify exactly how much the magnesium substitution enhances performance. Even with those caveats, the study demonstrates that a light-induced process makes a significant contribution to tetracycline removal and that a cheap, urea-assisted gel route carried out at just 700 degrees Celsius can deliver a phase-pure, crystalline spinel photocatalyst capable of attacking one of the most worrying classes of aquatic micropollutants. For an environmental challenge in which pharmaceutical effluents, particularly wash water from mixing tanks in drug and cosmetics manufacturing, can be highly concentrated and variable throughout the year, robust and adaptable treatment technologies are urgently needed, especially in developing countries where resources and advanced infrastructure remain limited. Alongside established approaches such as dense-membrane filtration, activated carbon adsorption and other advanced oxidation processes, this magnesium-substituted spinel now offers a low-cost candidate worth refining, one whose next iterations will need to probe different magnesium-to-zinc ratios, sunlight-driven operation and recyclability if it is to move from the laboratory beaker to real treatment trains.

Subject of Research: Magnesium-substituted zinc aluminate spinel photocatalysts for degrading tetracycline antibiotics in wastewater

Article Title: Facile preparation, characterization and photocatalytic activity of magnesium-substituted zinc aluminate

Article References: El Jabbar, Y., Lakhlifi, H., Talhajt, S. A., & El Ouatib, R. (2026). Facile preparation, characterization and photocatalytic activity of magnesium-substituted zinc aluminate. Results in Chemistry, 31, Article 103980. https://doi.org/10.1016/j.rechem.2026.103980

Image Credits: AI Generated

DOI: 10.1016/j.rechem.2026.103980

Keywords: photocatalysis, zinc aluminate, spinel, tetracycline, water treatment, pharmaceutical pollution, magnesium substitution, urea-assisted gel route, semiconductor, antibiotics, UV irradiation, wastewater

The findings arrive at a moment when the standard management of appendicitis is actively shifting. Over the past decade, antibiotic therapy has become an accepted alternative to the operating room for select patients, driven by trials showing that many uncomplicated cases resolve without surgery. That shift has largely been evaluated on short-term outcomes such as recurrence, complications, and quality of life. The new analysis raises a different question: whether leaving the appendix in place after an inflammatory episode carries long-term oncologic consequences that have so far gone unexamined.

Senior author Valentine Nfonsam, MD, MS, FACS, FASCRS, professor and executive vice chair of the department of surgery at Morehouse School of Medicine, said the motivation for the study grew out of that gap in the evidence. Antibiotic management remains an important option, he emphasized, but the discussion around nonoperative treatment has focused almost entirely on the immediate episode of appendicitis rather than on what may follow years later. The research team wanted to know whether the choice made in the emergency setting could shape cancer risk over the long arc of a patient’s life.

To answer that question, the investigators performed a retrospective cohort study using the TriNetX Global Collaborative Network, a federated database aggregating electronic health records from 168 health care organizations. They identified patients diagnosed with acute appendicitis who were treated either with an appendectomy or with antibiotics alone. After matching the two groups by baseline characteristics to reduce confounding, each treatment arm initially included 15,774 patients. Once the researchers excluded individuals who had received a colorectal cancer diagnosis before the study’s outcome period, the final cohorts comprised 15,616 appendectomy patients and 15,295 patients treated with antibiotics.

The numbers that emerged were striking. Colorectal cancer was diagnosed in 110 patients who had undergone appendectomy, or 0.7 percent of that group, compared with 254 patients treated with antibiotics alone, or 1.7 percent. After accounting for the matched design, the surgical group carried a 58 percent lower relative risk of a subsequent colorectal cancer diagnosis. Because the study is observational, it establishes an association rather than proof of causation, and the authors are careful about what the data can and cannot show. Still, the magnitude of the difference in a cohort of this size is difficult to dismiss as statistical noise.

Several biological explanations could account for the pattern, and the researchers outline them as hypotheses rather than conclusions. One possibility is detection bias in a favorable sense: an appendectomy gives surgeons a specimen for pathologic examination, and findings from that analysis can prompt additional diagnostic testing that might otherwise be delayed. In some patients, appendicitis may in fact be an early manifestation of an undiagnosed colorectal cancer rather than a precursor to one. An occult tumor on the right side of the colon, for example, can obstruct drainage from the appendix and first present as acute appendicitis, meaning the surgery may simply be unmasking disease that already exists.

A second line of explanation concerns the appendix itself, an organ long dismissed as a vestigial leftover of evolution. Emerging research suggests it plays an active role in the intestinal immune system and the gut microbiome, the community of bacteria and other microorganisms inhabiting the digestive tract. According to Nfonsam, the appendix contains a substantial amount of lymphoid tissue thought to contribute to immune functioning. Because alterations in inflammation and in the microbial environment have been linked to processes involved in colorectal cancer, the appendix’s biological functions represent a plausible area for further investigation. Removing the organ also eliminates a potential ongoing source of inflammation at the junction of the small and large intestines.

Nfonsam cautioned that the study cannot settle the mechanistic question. The appendix is rich in lymphoid tissue and participates in the local microbiome and immune system, he noted, and whether persistent inflammation or shifts in the microbial environment contribute to cancer development is biologically plausible, but the retrospective design cannot answer it directly. Distinguishing between the detection effect, the removal of an inflamed organ, and any true protective biology will require prospective work with longer follow-up and more granular clinical data.

The practical message from the researchers is not that every patient with appendicitis should undergo surgery to prevent cancer. Antibiotic management remains a legitimate and widely used option, and the absolute difference in cancer diagnoses, while meaningful, involves a small fraction of patients in both groups. Instead, the authors argue that treatment should not be one size fits all. Age, genetic predisposition, family history, and other established colorectal cancer risk factors may ultimately help clinicians select patients for nonoperative management and plan appropriate surveillance for those who choose it.

The research will be presented at the American College of Surgeons Clinical Congress 2026, held in Washington from September 26 to 29, where thousands of surgeons convene to advance surgical quality, patient safety, and access to care. The abstract was reviewed and selected by the congress program committee but has not yet undergone full peer review, a limitation the authors and the college both acknowledge. Co-authors on the work include Meghana Akula, Syed Fahad Gillani, Miriannie Rivera Valerio, Ahmad Zeineddin, Cassie Bowers, Miriam Michael, Quyen D. Chu, Christine E. Nembhard, and May C. Tee, and the authors report no disclosures. If the association holds up under peer review and prospective study, it could reshape how surgeons and patients weigh the long-term stakes of a decision that has, until now, been framed almost entirely in terms of the short-term recovery.

Subject of Research: Long-term colorectal cancer risk after appendectomy versus antibiotic treatment for acute appendicitis

Article Title: Appendectomy for appendicitis associated with 58% lower colorectal cancer risk than antibiotics alone

Article References: Appendectomy for appendicitis associated with 58% lower colorectal cancer risk than antibiotics alone. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: appendectomy, appendicitis, colorectal cancer, antibiotics, American College of Surgeons, gut microbiome, inflammation, cancer risk, retrospective cohort study, surgery, TriNetX, oncology

The review, led by Maria E. Ramos-Nino, Aniruddha Doshi, and Prakash V. A. K. Ramdass of St. George’s University in Grenada, followed PRISMA 2020 guidelines and searched PubMed/MEDLINE, Embase, Web of Science, and Google Scholar from database inception through August 31, 2026. The team screened 35 records, whittled them down through full-text assessment, and ultimately included just four human studies encompassing 384 participants at the study level, along with the animal component of one translational study. Risk of bias was evaluated with an adapted ROBINS-I framework for human observational studies and the SYRCLE tool for animal work, and certainty was graded using the GRADE framework. Because the studies differed so dramatically in anatomical compartment, detection method, and reported outcomes, the authors judged meta-analysis inappropriate and synthesized the findings qualitatively.

The heart of the controversy lies in two tissue-based studies that simply do not agree. The first, a 2023 translational study by Muraoka and colleagues in Japan, reported a striking signal: Fusobacterium was detected in 64.3 percent of endometrial samples from women with endometriosis compared with just 7.1 percent of controls in a 42-versus-42 tissue subset, and 52.4 percent of endometriotic lesions were also positive. The same group went further, showing in a mouse model that F. nucleatum exposure increased endometriotic lesion weight and promoted fibrosis associated with TGF-β signaling, effects that antibiotic treatment attenuated. That combination of human detection and experimental mechanism made headlines and fueled the oral microbe-host axis hypothesis.

But the second tissue study tells a very different story. Graciano-España and colleagues, working with the University of Pennsylvania Endomarker cohort, analyzed eutopic endometrium from 55 women with endometriosis and 37 controls using genus- and species-specific quantitative PCR. They found no significant difference in Fusobacterium species abundance between cases and controls, and no significant difference in F. nucleatum specifically. Subgroup analyses by disease severity were also null. The review notes that menstrual status was not uniform across groups, with a higher proportion of endometriosis cases menstruating at biopsy, but these differences do not by themselves explain the discordant results. In short, the strongest human tissue association has not been replicated.

The remaining two studies provide only indirect evidence because they never assessed endometrial or endometriotic tissue. Hicks and colleagues in Australia studied 64 participants and found oral Fusobacterium enrichment among patients with moderate or severe endometriosis compared with minimal or mild disease, while vaginal and stool samples showed no analogous signal. That anatomical specificity hints at a relationship between oral microbial composition and disease severity, but as the review emphasizes, it does not establish oral-to-reproductive-tract translocation or causality. Jimenez and colleagues in the United States examined vaginal and rectal microbiomes in women with chronic pelvic pain with and without endometriosis and found that F. animalis, historically classified as F. nucleatum subsp. animalis, was depleted in vaginal samples from the endometriosis group. No endometrial tissue was assessed, so this finding cannot be described as tissue-specific evidence for F. nucleatum.

Methodological heterogeneity is likely a major contributor to the divergent findings. The two tissue studies differed in population characteristics, disease phenotype, sampling procedures, menstrual status, DNA extraction approaches, and molecular targets. FISH provides spatial localization but its taxonomic specificity depends on probe design and hybridization conditions. Quantitative PCR offers sensitive targeted detection but hinges on primer specificity, extraction efficiency, and target selection. 16S rRNA sequencing profiles broader communities but may lack species-level resolution depending on the sequenced region and analytical pipeline. Anatomical sampling varied just as widely, from eutopic endometrium and endometriotic lesions to oral, vaginal, rectal, and stool samples, and evidence at one site cannot be assumed to reflect bacterial presence within lesions.

Contamination is an additional concern that the review treats seriously. Endometrial and endometriotic tissues are low-biomass specimens highly susceptible to reagent, environmental, and procedural contamination, and microbial signals generated this way can be difficult to distinguish from genuine tissue-associated bacteria. Inconsistent reporting of negative and procedural controls reduces confidence in some findings. Geographic and population differences may also contribute, since microbiome composition varies with diet, oral health, medication exposure, age, and disease stage. The emerging concept of an endobiota, which challenges the traditional view of the upper reproductive tract as sterile, makes rigorous contamination control all the more essential before any pathobiont can be credibly implicated.

The quality assessment is sobering. All four human observational studies were judged at serious overall risk of bias, driven primarily by potential confounding: adjustment for factors that could influence the microbiome, including antibiotic exposure, hormonal treatment, menstrual-cycle status, oral health, and comorbid gynecologic conditions, was incomplete or inconsistent across studies. Classification of endometriosis status was predominantly at low risk because surgical or histopathological confirmation was reported, but outcome measurement was rated moderate across studies because of differences in detection methods and potential contamination or taxonomic misclassification. For the animal experiments, the SYRCLE assessment found substantial uncertainty across most domains, with sequence generation, allocation concealment, random housing, and blinding all rated unclear because the relevant procedures were insufficiently reported. The GRADE assessment rated certainty of evidence as very low for every human and mechanistic outcome.

What does this mean for patients hoping that antibiotics might treat endometriosis? The review is unambiguous: the current evidence does not support antibiotic treatment based on presumed F. nucleatum involvement. Although antibiotic treatment reduced lesion burden and fibrosis in the experimental mouse model, these findings remain preclinical and have not been validated in randomized human trials. The authors also caution that evidence supporting antibiotic treatment of chronic endometritis, a distinct inflammatory condition, should not be extrapolated to endometriosis, whose bacterial etiology has not been established. Unnecessary antimicrobial exposure may promote resistance and disrupt commensal microbial communities, so antibiotics targeting F. nucleatum should not be recommended outside appropriately designed clinical trials.

Looking ahead, the review lays out a roadmap for testing the oral microbe-host axis properly. Future studies should use standardized, contamination-aware sampling protocols that define anatomical location, menstrual-cycle phase, recent antibiotic exposure, and oral-health status, with appropriate negative and environmental controls. Combining targeted methods such as qPCR or FISH with sequencing-based approaches in the same specimens could help separate methodological discrepancies from genuine biological variation. Critically, prospective studies should collect paired oral samples, preferably saliva and subgingival plaque, together with eutopic endometrium and endometriotic lesions, and apply strain-level genomic analyses to determine whether genetically related F. nucleatum strains occur in the oral cavity and reproductive tissues of the same individuals. Longitudinal designs are needed to establish whether bacterial presence precedes lesion development or occurs secondary to the altered inflammatory environment. Until such evidence exists, the review concludes, F. nucleatum should be regarded as a hypothesis-generating lead rather than an established cause or therapeutic target in endometriosis.

Subject of Research: The role of the oral bacterium Fusobacterium nucleatum in endometriosis

Article Title: The emerging oral microbe-host axis in endometriosis: a systematic review of Fusobacterium nucleatum

Article References: Ramos-Nino, M. E., Doshi, A., & Ramdass, P. V. A. K. (2026). The emerging oral microbe-host axis in endometriosis: a systematic review of Fusobacterium nucleatum. Frontiers in Cellular and Infection Microbiology, 16, Article 1994934. https://doi.org/10.3389/fcimb.2026.1994934

Image Credits: AI Generated

DOI: 10.3389/fcimb.2026.1994934

Keywords: endometriosis, Fusobacterium nucleatum, oral microbiome, systematic review, microbiome, fibrosis, TGF-β, endometrial tissue, microbial translocation, risk of bias, antibiotics, reproductive tract microbiome

The research team set out to qualitatively and quantitatively assess the antimicrobial efficacy of penicillin, gentamicin, vancomycin, rifampicin, kanamycin, ampicillin, clotrimazole, and amphotericin-B alongside essential oils from lemongrass (Cymbopogon flexuosus), palmarosa (Cymbopogon martinii), and peppermint (Mentha piperita). The pathogens under scrutiny included the Gram-positive bacteria Staphylococcus aureus, Staphylococcus epidermidis, Mycobacterium smegmatis, and Enterococcus faecalis, together with two fungal pathogens, Malassezia furfur and a clinical isolate of Candida albicans. These microorganisms are not exotic threats but everyday residents of the human skin, gut, and mucous membranes that can turn dangerous when the body’s homeostasis is disturbed by surgery, injury, malnutrition, immunodeficiency, or medication.

Opportunistic pathogens occupy a peculiar niche in medical microbiology. In an immunocompetent person, they live harmlessly as commensals, part of the vast microbial community that coexists in mutualistic association with the human body. But when the immune system is subverted or the normal balance of microflora is upset, these facultative parasites can escalate from mild infections to life-threatening bloodstream invasions. S. aureus, for instance, can circumvent immune defenses to cause carbuncles, folliculitis, cellulitis, abscesses, and bacteremia. S. epidermidis, which dwells predominantly on human skin, is a major culprit in hospital-acquired infections and infections of medical implants. E. faecalis, a gastrointestinal commensal, can trigger oral cavity infections, periodontitis, urinary tract infections, and nosocomial disease. Even M. smegmatis, which is not linked to tuberculosis in humans, has the potential to cause soft tissue and pulmonary infections in vulnerable patients.

On the fungal side, the study examined two dimorphic and polymorphic pathogens. C. albicans, an exclusively opportunistic fungus, is well known for causing oral, cutaneous, and vulvovaginal candidiasis, as well as candidaemia and hospital-acquired infections. M. furfur, isolated in this study from a human scalp, is associated with skin conditions such as dandruff, seborrheic dermatitis, and pityriasis versicolor. Combatting these infections traditionally requires reliance on synthetic or semi-synthetic antimicrobials spanning classes such as β-lactams, aminoglycosides, glycopeptides, quinolones, azoles, and polyenes. Yet the indiscriminate use of these drugs has fueled the emerging phenomenon of antibiotic resistance and can carry harmful effects on essential organs, prompting researchers to explore natural alternatives.

Methodologically, the study employed two complementary assays. The disk diffusion test involved spreading 100 microliters of microbial suspension evenly onto fresh nutrient or Sabouraud agar plates, then placing 5-millimeter filter paper disks loaded with 5 micrograms of standard antimicrobials or 30 microliters of essential oil. After incubation at 37 degrees Celsius for 24 hours for bacteria and 28 degrees Celsius for 48 hours for fungi, clear zones of growth inhibition were measured in millimeters, with each test performed in triplicate. The minimum inhibitory concentration, or MIC, was determined by broth dilution in 96-well microtiter plates, with cultures adjusted to 0.5 McFarland standard turbidity to obtain 1 × 10^8 colony-forming units per milliliter. A redox indicator dye, shifting from purple to pink in the presence of cellular reductases, provided a visual readout of microbial viability. The minimum bactericidal and fungicidal concentrations were deduced by spot inoculation onto fresh agar plates from the last three wells of each dilution series.

The disk diffusion results exposed the patchy nature of synthetic drug efficacy. Penicillin produced the maximum zone of inhibition against S. aureus at 40.0 millimeters and suppressed E. faecalis with a 33.0-millimeter zone, while rifampicin and ampicillin also generated strong zones against S. aureus at 32.0 and 32.3 millimeters respectively. Gentamicin proved the most favorable drug against S. epidermidis and M. smegmatis, each at roughly 19 to 20 millimeters. Yet penicillin and ampicillin were completely inactive against M. smegmatis, and S. epidermidis showed no response to penicillin, vancomycin, or ampicillin. Vancomycin, often considered a drug of last resort for Gram-positive infections, exhibited activity against three of the four tested bacteria but proved ineffective against S. epidermidis. Among the antifungals, clotrimazole was highly effective against both M. furfur and C. albicans, producing zones of 34.0 and 32.0 millimeters respectively, while amphotericin-B showed more modest inhibition at 17.5 and 18.0 millimeters.

The essential oils told a different story. Lemongrass oil, applied at 3 percent volume per volume, displayed prominent zones of inhibition against every pathogen examined, including the strains resistant to conventional antibiotics. Its zones ranged from 12.7 millimeters against S. aureus to 30.3 millimeters against M. smegmatis, with particularly strong activity against the fungal pathogens at 27.0 and 28.3 millimeters for M. furfur and C. albicans respectively. Peppermint oil was most effective against M. smegmatis at 31.7 millimeters, while palmarosa oil showed its highest inhibition against M. furfur at 16.7 millimeters. Notably, M. smegmatis, which was resistant to penicillin and ampicillin, was prominently inhibited by both lemongrass and peppermint oils. A similar pattern emerged against S. epidermidis, though peppermint oil showed very low inhibition in that case.

The MIC data reinforced these findings with quantitative precision. Penicillin and rifampicin inhibited S. aureus and E. faecalis at an MIC of 0.10 micrograms per milliliter, while gentamicin suppressed S. epidermidis and M. smegmatis at the same concentration. Kanamycin required a higher MIC of 0.39 micrograms per milliliter to restrict S. epidermidis, and vancomycin was effective at slightly higher concentrations for all pathogens except E. faecalis. Clotrimazole showed antifungal activity at an MIC of 0.10 micrograms per milliliter for both fungal pathogens, whereas amphotericin-B required a higher concentration of 3.12 micrograms per milliliter. For the essential oils, palmarosa yielded the most favorable results against the bacterial pathogens, with MIC values ranging from 0.07 to 0.09 percent volume per volume. Peppermint oil was particularly effective against S. aureus at 0.07 percent, while lemongrass required slightly higher concentrations at 0.19 percent. Against the fungal pathogens, palmarosa and peppermint oils inhibited both at 0.3 percent, while lemongrass achieved inhibition at just 0.12 percent. Crucially, the minimum bactericidal concentrations aligned with the MIC values, indicating that the oils were not merely suppressing growth but killing the pathogens outright.

The mechanistic explanation for essential oil activity lies in their complex bioactive composition. These natural extracts contain a wide variety of terpenes and phenolic compounds whose antimicrobial mode of action relies mainly on cell membrane disruption, interference with enzymatic activity, inhibition of cellular respiration, and disruption of DNA and RNA synthesis. Because these mechanisms target multiple cellular structures simultaneously rather than a single molecular target, pathogens pose minimal risk of developing resistance through the routes that plague conventional antibiotics, such as target alteration or the development of efflux pumps to expel the drug. Combined with their low toxicity, economic viability, and biodegradability, essential oils may be better suited as medications in contrast to synthetic antimicrobials, particularly in an era when multidrug-resistant pathogens have become a serious threat to existing antibacterial treatment.

The authors conclude that although the antimicrobial potency of essential oils cannot surpass standard antibiotics in absolute terms, their efficacy managed to align with synthetic drugs even when differing concentrations were taken into account. All three essential oils inhibited the growth of all tested pathogens to some degree, contrary to several antibiotics that failed to suppress the proliferation of specific microorganisms. Lemongrass oil depicted the most favorable results, giving distinct zones of inhibition between 12.7 and 30.3 millimeters for the majority of tested pathogens while remaining efficient toward resistant strains. The researchers caution that additional research under in vivo conditions is needed to thoroughly assess the full therapeutic potential of these oils and provide valuable insights into potential treatments as substitutes against relevant diseases. Yet the message is clear: nature’s pharmacy, refined over millions of years of plant evolution, may hold answers that synthetic chemistry alone cannot provide.

Subject of Research: Comparative antimicrobial efficacy of synthetic antibiotics and plant essential oils against human pathogenic bacteria and fungi

Article Title: Comparative antimicrobial evaluation of synthetic antibiotics and essential oils against human pathogenic bacteria and fungi

Article References: Khaliq, A., Mishra, A. K., & Rabbani, A. (2024). Comparative antimicrobial evaluation of synthetic antibiotics and essential oils against human pathogenic bacteria and fungi. Innovations in Agriculture, 7, 1-7. https://doi.org/10.3897/ia.2024.124222

Image Credits: AI Generated

DOI: 10.3897/ia.2024.124222

Keywords: antimicrobial resistance, essential oils, lemongrass, antibiotics, Candida albicans, Staphylococcus aureus, natural remedies, disk diffusion assay, Comparative, antimicrobial, evaluation, synthetic

The research, led by María Emilia Zelaya-Soulé of the National University of Luján and published in Environmental Science and Pollution Research, set out to evaluate how well montmorillonite and two montmorillonite–carbon hybrid materials remove oxytetracycline from water under both controlled and deliberately complicated conditions. Montmorillonite, a naturally abundant swelling clay, has long been known to bind tetracycline antibiotics through cation exchange and other interactions at its negatively charged surfaces. The hybrids used in this work combine that clay with carbon derived from carbohydrates, creating composite materials that merge the ion-exchange chemistry of the mineral with the hydrophobic, structurally heterogeneous adsorption sites of carbon. The idea is simple in principle: if you can fuse the binding strengths of two very different classes of surfaces into one material, you should get an adsorbent that works across a broader range of pollutant chemistries and water conditions than either component alone.

The team began with the classic controlled experiments. Using batch adsorption tests, they measured how much oxytetracycline each material could remove as a function of contact time, concentration, and pH, fitting the data to kinetic and equilibrium models to extract mechanistic information. The results were striking. One of the hybrids, designated MDac3-210–500, achieved a maximum adsorption capacity of approximately 0.6 millimoles per gram at neutral pH, a figure that places it among the more capable clay-based adsorbents reported for this class of antibiotics. At neutral pH, oxytetracycline exists as a mixture of zwitterionic and anionic species, and the hybrid’s carbon-rich surfaces appear to provide the right combination of hydrophobic domains and polar functional groups to capture these molecules efficiently.

Mechanistic analysis of the kinetic data revealed something important about how the two classes of materials actually work. For plain montmorillonite, the adsorption behavior was consistent with chemisorption playing a dominant role, meaning that the antibiotic forms relatively strong chemical bonds with specific sites on the clay surface rather than simply sticking through weak physical forces. For the hybrids, by contrast, the data pointed toward intraparticle diffusion and surface heterogeneity as the controlling factors. In other words, the rate-limiting step is not the formation of a chemical bond but the physical journey of antibiotic molecules diffusing into the porous interior of the carbon–clay composite, where they encounter a patchwork of binding sites with varying affinities. This distinction matters for engineers because it suggests the hybrids behave more like sponges with distributed capture zones, while the clay behaves more like a surface with a finite set of high-affinity anchors.

But the researchers did not stop at the clean-water benchmark. They recognized that in the real world, oxytetracycline almost never arrives alone. When farmers administer the antibiotic to livestock, they typically use commercial veterinary formulations that contain not just the active molecule but a suite of additives, stabilizers, solubilizers, and preservatives designed to keep the drug effective in the bottle. These additives, though chemically minor compared to the active ingredient, can be highly competitive adsorbates in their own right. To approximate this reality, the team repeated their adsorption experiments using an actual veterinary commercial oxytetracycline formulation rather than the pure analytical standard.

The outcome was dramatic. In the presence of the commercial formulation, the adsorption capacity of the hybrid materials plummeted to between 0.05 and 0.08 millimoles per gram, a reduction of roughly 90 percent compared to the clean-water maximum. The interpretation is that the formulation additives compete directly with oxytetracycline for the same active sites on the hybrid surfaces, effectively crowding the antibiotic out of its preferred binding zones. This is a textbook example of what adsorption scientists call matrix effects, where the chemical complexity of the surrounding solution fundamentally alters how an adsorbent performs. The finding carries a sobering implication: laboratory tests that use only pure analytical standards may dramatically overestimate how well a given adsorbent will work in a real treatment scenario, because they ignore the molecular competition that inevitably arises from coexisting compounds.

Yet the study contained a genuine surprise in the opposite direction. Microplastics, particularly polyethylene terephthalate or PET, have become one of the most discussed co-contaminants in water treatment research, with numerous studies suggesting that plastic particles can either compete with antibiotics for adsorbent sites or even act as carriers that concentrate pollutants and transport them through the environment. The Argentine team tested this directly by adding PET microplastics smaller than 112 micrometers at a concentration of 0.5 grams per liter to their adsorption experiments. Under the conditions tested, the PET particles did not substantially modify oxytetracycline adsorption by the hybrid materials. The contrast with the commercial formulation could hardly be sharper: one coexisting contaminant devastated performance, while the other, at least in this experimental setup, was essentially neutral.

The authors are careful to note that this neutrality applies to the specific conditions they tested, including the particular particle size, concentration, and degree of aging of the PET microplastics. Other research has shown that weathered or photoaged microplastics can develop increased surface functionality and stronger interactions with antibiotics, and that smaller particles at higher concentrations might behave differently. But the finding still matters because it suggests that not every coexisting contaminant deserves equal weight when evaluating adsorbent performance. The molecular identity and concentration of coexisting compounds, not simply their presence, determine whether they will interfere with treatment. Formulation additives, being small, soluble, and chemically similar to the target antibiotic, turn out to be far more dangerous competitors than relatively inert plastic particles.

What makes this study particularly valuable is that it provides a quantitative basis for thinking about adsorbent performance under realistic water chemistry rather than idealized conditions. The sensitivity of oxytetracycline adsorption to coexisting compounds, as the authors put it, emphasizes the importance of considering matrix composition when evaluating any adsorbent material. For engineers designing water treatment systems for livestock operations, veterinary clinics, or agricultural runoff, the message is clear: the performance of a clay–carbon hybrid measured against a pure standard tells only part of the story. The real test is how that material behaves when the antibiotic arrives packaged with the very additives that make it usable in the first place.

The broader significance extends beyond oxytetracycline itself. Tetracycline antibiotics are among the most detected pharmaceuticals in surface waters and groundwater worldwide, and their persistence fuels the spread of antimicrobial resistance, a problem the World Health Organization has identified as one of the top global public health threats. Clay–carbon hybrids, being built from abundant natural montmorillonite and renewable carbohydrate-derived carbon, offer a potentially scalable and low-cost route to removing such pollutants. But this research shows that the path from laboratory promise to real-world impact runs directly through the messy chemistry of actual contaminated water, where additives, plastics, dissolved organic matter, and countless other coexisting species all compete for the same limited binding sites. Understanding which of those competitors matter most, and by how much, is the kind of unglamorous but essential knowledge that turns a promising material into a working technology.

Subject of Research: Removal of the antibiotic oxytetracycline from water by montmorillonite and clay–carbon hybrid adsorbents under realistic conditions including formulation additives and PET microplastics

Article Title: Oxytetracycline adsorption by clay–carbon hybrids: effects of pH, commercial formulation additives, and PET microplastics

Article References: Zelaya-Soulé, M. E., Montes, M. L., Villanueva, M. E., & Fernández, M. A. (2026). Oxytetracycline adsorption by clay–carbon hybrids: effects of pH, commercial formulation additives, and PET microplastics. Environmental Science and Pollution Research. https://doi.org/10.1007/s11356-026-38315-5

Image Credits: AI Generated

DOI: 10.1007/s11356-026-38315-5

Keywords: oxytetracycline, clay–carbon hybrids, montmorillonite, adsorption, antibiotics, water treatment, PET microplastics, formulation additives, matrix effects, Environmental Science and Pollution Research, clay, carbon

The research team, led by M. Nazmul Hoque and M. Shaminur Rahman of Gazipur Agricultural University, collected milk samples from 20 lactating crossbred dairy cows on a commercial farm in the Dhaka district. Ten cows tested positive for subclinical mastitis using the California Mastitis Test, a diagnostic tool that detects elevated somatic cell counts without requiring visible signs of infection. These same 10 animals were then treated with a seven-day course of intramuscular ampicillin, a beta-lactam antibiotic, and azithromycin, a macrolide, the two most frequently administered antibiotics in dairy animals in Bangladesh. Milk samples were collected 24 hours after the final antibiotic injection, while milk from 10 healthy, untreated cows served as controls. The study design allowed the researchers to compare three distinct conditions: subclinical mastitis milk, antibiotic-treated milk, and healthy milk, each represented by 10 samples.

The sequencing effort was substantial. The team generated 327 million raw reads across all 30 samples, averaging 10.9 million reads per sample, using an Illumina NovaSeq 6000 platform. After rigorous quality control, adapter trimming, and removal of host-derived sequences using the Bos taurus reference genome, the researchers retained 94 to 99 percent of reads for microbial analysis. Taxonomic profiling was performed using Kraken2 with a custom database, while functional profiling of resistance determinants and metabolic pathways was conducted using the AMR++ pipeline aligned against the MEGARes v2.0 database and HUMAnN3 for KEGG pathway reconstruction. The bioinformatics workflow included negative extraction controls to monitor for reagent contamination, and any putative microbial or resistance gene signals detected in these controls were rigorously subtracted from the sample data sets.

The results revealed a striking pattern of microbial dysbiosis. Healthy milk samples exhibited the highest microbial richness, with a median of 129.5 observed taxa and a Shannon diversity index of 1.59. In contrast, subclinical mastitis milk showed reduced richness at 68.5 taxa and a Shannon diversity of 1.14, while antibiotic-treated milk had the lowest richness at 51.5 taxa, though its Shannon diversity of 1.41 was slightly higher than that of mastitis milk. Pairwise comparisons confirmed that healthy milk was significantly more diverse than both mastitis milk and antibiotic-treated milk. Interestingly, breed type also influenced diversity, with Local Zebu cows showing the highest richness at 142 taxa, followed by Holstein Friesian Cross at 101 and Sahiwal Cross at 81. Age-related trends showed that middle-aged cows between 5 and 8 years exhibited peak diversity, significantly higher than both younger and older animals.

At the phylum level, the bacteriome was dominated by three major groups: Pseudomonadota, Actinomycetota, and Bacillota, which collectively accounted for 90 to 99 percent of total bacterial abundance. Pseudomonadota was more abundant in antibiotic-treated milk at 51.75 percent and healthy milk at 40.57 percent compared to mastitis milk at 37.80 percent. Actinomycetota was enriched in mastitis milk at 40.67 percent and healthy milk at 32.80 percent, while Bacillota was highest in healthy milk at 16.19 percent. The persistence of Pseudomonadota in antibiotic-treated samples is clinically concerning because this phylum encompasses opportunistic pathogens including Escherichia coli, Klebsiella pneumoniae, and Acinetobacter johnsonii, all recognized mastitis agents. The researchers suggest that conventional antibiotic therapy may not effectively suppress these taxa, potentially due to biofilm formation, acquired resistance mechanisms, or the presence of persister cells that survive antimicrobial exposure.

At the species level, the study identified 665 bacterial species across all samples, with 471 detected in healthy milk, 272 in antibiotic-treated milk, and only 202 in mastitis milk. Just 26 species, or 3.91 percent, were shared across all three groups. Actinoalloteichus sp. and Vibrio furnissii emerged as the two most abundant species in the antibiotic-treated group, together accounting for over 70 percent of the total community. Staphylococcus aureus, a key mastitis-associated pathogen, was markedly enriched in mastitis milk at 1.74 percent relative abundance but nearly absent in healthy and antibiotic-treated samples. Conversely, A. johnsonii peaked in antibiotic-treated milk at 10.52 percent but was almost absent in mastitis milk, suggesting that the active mastitic microenvironment is unfavorable to its survival until antibiotic pressure suppresses competing taxa. Beneficial commensals such as Pseudomonas lundensis and Bacteroides thetaiotaomicron were heavily depleted or entirely absent in both mastitis and antibiotic-treated samples, confirming that disease-associated dysbiosis involves the severe displacement of organisms vital for maintaining udder homeostasis.

The resistome analysis revealed an even more alarming picture. The researchers identified 194 distinct antimicrobial resistance genes across all samples, with the majority detected in mastitis-associated microbiomes at 161 genes, followed by antibiotic-treated milk at 51 genes and healthy milk at just 24 genes. Mastitis milk possessed the largest fraction of unique resistance genes at 68.04 percent, cementing the unmanaged mastitic udder as a massive natural reservoir for diverse resistance determinants. In antibiotic-treated samples, macrolide resistance genes dominated, particularly the 23S rRNA mutation, reflecting strong selection pressure from clinical macrolide use. Aminoglycoside resistance mechanisms, including 16S ribosomal mutations and protective ribosomal proteins, were similarly enriched in antibiotic-treated milk, confirming treatment-associated resistance development. The strong positive correlation between macrolide and aminoglycoside resistance in antibiotic-treated milk indicates co-selection of resistance mechanisms under therapeutic pressure, where exposing the microbiome to one drug simultaneously selects for linked resistance mechanisms.

Correlation analysis identified key bacterial taxa that serve as major reservoirs for specific resistance genes. E. coli emerged as a prominent multi-resistance hub, displaying strong positive associations with tetracycline resistance genes, aminoglycoside resistance determinants, and multidrug efflux pump systems. A. johnsonii was strongly coupled with aminoglycoside resistance and beta-lactamase genes, which explains its competitive dominance in antibiotic-treated milk following therapeutic exposure. K. pneumoniae similarly acted as a resistance hub for efflux systems and tetracycline resistance. The community-dominating taxa Actinoalloteichus sp. and V. furnissii maintained broad baseline positive correlations across nearly all major resistance gene classes, including beta-lactams, macrolides, and tetracyclines, likely underpinning their ability to remain completely unsuppressed during active antibiotic treatment. Even healthy milk samples contained background reservoirs of resistance factors carried by commensals, including tetracycline and elfamycin resistance genes, emphasizing that the baseline milk microbiome naturally harbors low-level resistance determinants even in the absence of disease or therapeutic intervention.

Functional profiling using KEGG pathway reconstruction further clarified the adaptive mechanisms employed by the bacteriome during dysbiosis. Acinetobacter and Pseudomonas species displayed consistent positive correlations with core metabolic pathways, specifically membrane transport, amino acid metabolism, lipid metabolism, and xenobiotic biodegradation. This metabolic versatility is highly indicative of enhanced stress tolerance, as upregulating membrane transport and lipid catabolism allows these Gram-negative taxa to actively detoxify their microenvironment and drive cellular efflux, facilitating survival in antibiotic-exposed settings. In sharp contrast, S. aureus exhibited negative correlations with these core metabolic pathways while correlating positively with host-interactive processes, suggesting that this pathogen relies on specialized virulence factors rather than broad metabolic adaptability. The tightly coupled gut-associated commensal consortium demonstrated uniform positive links with carbohydrate metabolism, replication and repair, and biosynthesis of secondary metabolites, reflecting a stable homeostatic lifestyle focused on energy harvesting rather than stress-induced detoxification.

The study’s findings carry significant implications for antimicrobial stewardship in the dairy sector. The researchers emphasize that routine monitoring of antimicrobial resistance and judicious antibiotic use are urgently needed to curb resistance within dairy systems in Bangladesh and comparable settings. They also note that breed and age serve as additional modulatory factors, with Local Zebu cows and middle-aged animals maintaining the healthiest microbial profiles. However, the authors acknowledge several limitations, including the single-farm design, small group sizes, the combined ampicillin-azithromycin regimen that prevents assessment of each drug’s independent effects, and the collection of antibiotic-treated samples only 24 hours after the final dose, which may reflect acute drug exposure rather than persistent ecological changes. Future longitudinal, multi-farm studies integrating somatic cell counts, culture-based confirmation, metatranscriptomics, and metabolomics will be needed to validate these findings and clarify the mechanisms linking microbiome, resistome, and metabolic dynamics in bovine mastitis.

Subject of Research: Milk microbiome and antibiotic resistance genes in dairy cows with subclinical mastitis

Article Title: Subclinical Mastitis and Antibiotic Exposure Reshape the Milk Bacteriome, Resistome, and Metabolic Functional Profiles in Dairy Cows

Article References: Hoque, M. N., Rahman, M. S., Hossain, M. G., Rahman, M. T., Islam, T., & Hossain, M. A. (2026). Subclinical Mastitis and Antibiotic Exposure Reshape the Milk Bacteriome, Resistome, and Metabolic Functional Profiles in Dairy Cows. MicrobiologyOpen, 15(5), Article e70440. https://doi.org/10.1002/mbo3.70440

Image Credits: AI Generated

DOI: 10.1002/mbo3.70440

Keywords: dairy cows, mastitis, milk microbiome, antimicrobial resistance, metagenomics, antibiotics, Subclinical, Antibiotic, Exposure, Reshape, Milk, Bacteriome

The core rationale behind post-marketing safety evaluation lies in a fundamental statistical limitation of randomized controlled trials. Because trials typically enroll hundreds to a few thousand participants over limited follow-up periods, they are powered to detect common adverse events but systematically exclude rare or long-term harms that may only emerge once a drug reaches tens of thousands of patients. Two of the studies in the Research Topic addressed this gap by mining the FDA Adverse Event Reporting System, or FAERS, a database containing millions of spontaneous reports submitted by healthcare professionals, manufacturers, and patients. Spontaneous reporting databases are noisy by nature, but when analyzed with disproportionality methods, which compare the observed frequency of a drug-event pair against its expected background frequency, they can reveal genuine safety signals hidden in the statistical structure of the reports.

The first of these pharmacovigilance analyses, led by Xie and colleagues, focused on oritavancin, a long-acting lipoglycopeptide antibiotic used against serious gram-positive infections including methicillin-resistant Staphylococcus aureus. The study corroborated known safety signals such as chills and infusion-related reactions, but it also identified multiple underemphasized or entirely unlabeled signals, including dyspnea, chest discomfort, and anaphylactic reactions. Particularly striking was the temporal pattern of the reports: the majority of adverse events occurred within the first few days of treatment. This finding underscores the need for intensified vigilance during the earliest phase of therapy, a window that clinicians may overlook when a drug has already passed regulatory review and entered routine use.

A second FAERS-based study by Li and colleagues applied disproportionality and Bayesian analysis to a newer class of tetracycline derivatives, examining coagulation dysfunction associated with tigecycline, eravacycline, and omadacycline. The analysis identified reporting signals for tigecycline and eravacycline, including hypofibrinogenemia and prolonged prothrombin time, which emerged as the predominant coagulation abnormalities across the three antibiotics. Omadacycline, by contrast, showed a generally more favorable coagulation profile, although discrete positive signals for hypofibrinogenemia appeared in subgroup analyses. The distinction matters clinically because coagulation abnormalities can escalate into serious bleeding events, and recognizing which members of a drug class carry the highest risk allows prescribers to weigh alternatives more precisely, particularly in patients already vulnerable to bleeding complications.

Beyond drug safety, the Research Topic also explored how pharmaceutical sales data can function as an early warning system for respiratory infectious disease outbreaks. Li and colleagues investigated the effectiveness of over-the-counter pharmaceutical sales as a timely indicator for predicting respiratory infection trends in Pinghu, China. The underlying logic is that people typically self-medicate at the first appearance of symptoms, well before they seek hospital care or receive a confirmed diagnosis. By monitoring sales of cough suppressants, antipyretics, and other over-the-counter remedies, public health authorities can detect potential outbreaks before confirmed hospital data become available, enabling better medical resource allocation and more rapid epidemic responses. The authors cautioned, however, that such sales signals should be integrated with other data sources, including school absence records and online search queries, to improve early monitoring and overall surveillance accuracy, since sales patterns alone can be distorted by seasonal purchasing behavior and marketing effects.

Drug resistance surveillance formed another pillar of the collection. Zhang and colleagues investigated resistance mutations in people living with HIV experiencing low-level viremia in Chongqing, China, a clinical scenario in which standard genotyping often fails because viral loads are too low for conventional RNA-based assays. By employing a combined strategy that genotyped both plasma RNA and proviral DNA integrated into the host genome, the team detected resistance mutations in 26.32 percent of the cohort, predominantly against non-nucleoside reverse transcriptase inhibitors. Low baseline CD4-positive T-cell counts below 100 cells per microliter were significantly associated with the presence of resistance. The combined genotyping strategy enhanced resistance detection even when viral load was minimal, demonstrating its value for resistance surveillance and for optimizing clinical management in patients whose treatment failure would otherwise go undetected until viremia rebounded to higher levels.

Adjunctive disease management was the focus of a meta-analysis by Nie and colleagues, who evaluated the role of supplementary therapies for recurrent rhinosinusitis, a condition in which standard treatment alone often fails to prevent repeated episodes. The analysis examined nasal irrigation, steroid-eluting implants, and concurrent dental management, and found that these modalities produced a 30 to 50 percent improvement in symptom scores measured with validated instruments such as the Sino-Nasal Outcome Test, alongside reduced recurrence rates compared with conventional treatment alone. The findings support a multimodal, patient-centered approach to disease management, in which mechanical, pharmacological, and dental interventions work in concert rather than in isolation, reflecting a broader trend in infectious disease care toward combination strategies that address the anatomical and behavioral factors driving chronic recurrence.

The long-term impact of immunization programs rounded out the Research Topic. Liu and colleagues analyzed the epidemiological characteristics and vaccine effectiveness of pertussis vaccination in Linping District, China. The diphtheria-tetanus-acellular pertussis vaccine series provided high protection, exceeding 90 percent effectiveness for children through the preschool age. However, the study identified a distinct spring peak in incidence, and delayed or missed vaccination emerged as a key risk factor for infant cases. The findings suggest that waning immunity after the primary series may necessitate evaluation of booster doses at school age, a consideration that aligns with international experience showing that acellular pertussis vaccines induce strong but non-durable protection whose decay can leave adolescents and adults susceptible to infection and capable of transmitting the bacterium to unvaccinated infants.

Henriquez-Camacho concludes that pharmacoepidemiology provides indispensable insights into the real-world use and impact of infectious disease interventions, thereby ensuring safe, effective, and equitable healthcare strategies. The editorial emphasizes that the discipline’s integration with emerging technologies and global data networks will further enhance preparedness for future health crises. As the six studies demonstrate, whether the question is an unlabeled anaphylaxis signal for a newly approved antibiotic, a coagulation risk hidden within a drug class, an outbreak brewing behind rising pharmacy sales, a resistance mutation at undetectable viral load, or the slow decay of vaccine-induced immunity, population-scale data analysis consistently reveals what trials cannot. In an era of rising antimicrobial resistance and recurring epidemic threats, that capacity to see the full picture of drug use and disease control at the population level has never been more essential.

Subject of Research: Pharmacoepidemiology in infectious diseases

Article Title: Editorial: Pharmacoepidemiology in infectious diseases

Article References: Henriquez-Camacho, C. (2026). Editorial: Pharmacoepidemiology in infectious diseases. Frontiers in Antibiotics, 5, Article 1965761. https://doi.org/10.3389/frabi.2026.1965761

Image Credits: AI Generated

DOI: 10.3389/frabi.2026.1965761

Keywords: pharmacoepidemiology, infectious diseases, pharmacovigilance, FAERS, antibiotics, drug resistance, vaccine effectiveness, public health, Editorial, infectious, diseases, scientific research

The study’s central figure is sulfachloropyridazine, a veterinary sulfonamide antibiotic that dominated the pollution profile of one tributary. At a single sampling point downstream of an intensive livestock farm, SCP reached an annual average concentration of 18,288 nanograms per liter in one river section, a level that far exceeds the typical surface water concentrations of under 1,000 nanograms per liter reported in global surveys. The peak measurement of 36,577 nanograms per liter represents one of the highest antibiotic concentrations documented in a natural river system, and the compound’s ecological risk quotient averaged 18.92 across three consecutive sampling points, placing it firmly in the high-risk category under standard assessment frameworks.

What makes the finding particularly significant is the spatial structure the researchers uncovered. Rather than a uniform gradient of contamination from upstream to downstream, the basin contained two spatially independent pollution hotspots separated by a stretch of river with background concentrations below 50 nanograms per liter. The first hotspot, located on a major tributary, was dominated almost entirely by SCP and exhibited what the authors describe as a high-intensity, rapid-attenuation pattern, with concentrations falling sharply within a few kilometers of the source. The second hotspot, on a different tributary, was characterized by sulfamethoxazole and florfenicol at more moderate concentrations that declined slowly along the flow path, a signature the researchers associate with urban sewage inputs rather than agricultural runoff.

This distinction matters because it demonstrates that antibiotic pollution in a single watershed can arise from fundamentally different sources with fundamentally different environmental behaviors. Sulfonamides and tetracyclines are typically linked to livestock and aquaculture operations, where they are used as feed additives and therapeutic agents, while macrolides and fluoroquinolones tend to originate from human medical use and enter waterways through domestic sewage and hospital wastewater. The researchers used principal component analysis of the 15 detected antibiotics to separate samples dominated by SCP from those dominated by azithromycin and erythromycin, confirming that the two pollution zones were statistically distinct rather than points along a single contamination gradient.

Beyond mapping where the pollution was, the team went a step further and quantified how fast it disappeared. Using a first-order kinetic model fitted to the logarithm of concentration plotted against downstream distance, they calculated apparent attenuation coefficients for SCP in the river section where it peaked. The values ranged from 0.28 to 2.24 per kilometer, with the highest rates observed during the wet season of 2024 and the lowest during the dry season. The researchers attribute this seasonal difference to stronger hydrodynamic mixing during high-flow periods, which enhances dilution and promotes the photolysis and hydrolysis reactions that break down sulfonamide molecules. The coefficients of determination for the regression models were remarkably high, ranging from 0.901 to 0.998, indicating that the first-order decay model described the observed patterns well despite the inherent complexity of natural river systems.

The authors are careful to note that these attenuation coefficients are apparent field-scale estimates rather than intrinsic degradation rate constants. They integrate dilution, hydrodynamic mixing, sorption to sediments, photolysis, and biodegradation into a single number, and they may represent upper-bound estimates because diffuse agricultural inputs between sampling points cannot be entirely excluded. The confidence intervals are also relatively wide, reflecting the limited number of sampling points used in each regression. Nevertheless, the study represents the first quantitative estimation of SCP attenuation in a river in eastern China, and the researchers note that a search of the Web of Science database returned only 48 publications on sulfachloropyridazine in surface water compared with more than 13,000 on antibiotics generally, highlighting how little attention this compound has received despite its apparent environmental significance.

The ecological risk assessment revealed a pattern of risk that was highly localized rather than basin-wide. Most antibiotics posed negligible risk across most of the river network, but at the SCP hotspot the risk quotient reached levels nearly 19 times the threshold for high concern. Sulfathiazole and azithromycin showed moderate to low risk across multiple consecutive river sections, forming what the researchers describe as a background risk spectrum. By 2025, the overall risk profile had moderated, with no high-risk points detected, though sulfathiazole and sulfameter both fell into the moderate risk category at several locations and SCP continued to pose moderate risk in multiple river sections. The researchers caution that their assessment evaluated each antibiotic individually and did not account for mixture toxicity, meaning the true ecological risk may be underestimated where multiple compounds co-occur.

One of the most practical contributions of the study is a prioritization framework that could reshape how monitoring resources are allocated. Of the 32 antibiotics screened, 14 were never detected at all and 10 more appeared at consistently low detection frequencies below 20 percent with risk quotients below 0.1, allowing the researchers to recommend excluding 24 compounds, or 75 percent of the target list, from routine monitoring. The remaining eight antibiotics warrant focused attention, with SCP identified as the core risk indicator for agricultural hotspots and sulfamethoxazole and florfenicol prioritized in urban-influenced sections. The framework is spatially adaptive rather than uniform, meaning that monitoring priorities shift depending on land use and pollution source characteristics within each river section, an approach the authors say has not previously been applied at the river basin scale.

The researchers recommend that the 24 deprioritized compounds be reassessed every two to three years, or immediately following significant land-use changes, to confirm that they remain at negligible levels. They also emphasize that their source identification relies on spatial coincidence and land-use correlation rather than formal source apportionment techniques such as positive matrix factorization or stable isotope analysis, so the management recommendations should be regarded as provisional until quantitative source attribution is available. Still, the circumstantial evidence is compelling: the sampling point with the highest SCP concentration sits directly downstream of an intensive livestock farm, and the compound is widely used as a veterinary feed additive and therapeutic agent.

The broader significance of this work lies in its demonstration that even as overall water quality improves across large regions, concentrated point sources and localized non-point pollution from intensive agriculture can still create pockets of extreme ecological risk that basin-wide averages completely obscure. The high-resolution spatiotemporal dataset and the attenuation coefficients generated here provide a scientific foundation for targeted interventions, whether that means enhanced livestock waste management at agricultural hotspots or improved sewage treatment in urban-influenced zones. For regulators facing limited monitoring budgets, the message is clear: a smaller, smarter list of target compounds, applied with spatial awareness, can detect the pollution that matters most while cutting analytical costs by more than 70 percent.

Subject of Research: Occurrence, spatiotemporal distribution, and ecological risks of 32 antibiotics in a river basin of eastern China

Article Title: Occurrence, spatiotemporal distribution, and ecological risks of antibiotics in a river basin of eastern China

Article References: Lin, X., Wang, J., Liu, Z., Zhou, J., Sun, Q., Chen, S., & Hu, H. (2026). Occurrence, spatiotemporal distribution, and ecological risks of antibiotics in a river basin of eastern China. Environmental Monitoring and Assessment, 198(11), Article 1204. https://doi.org/10.1007/s10661-026-16036-z

Image Credits: AI Generated

DOI: 10.1007/s10661-026-16036-z

Keywords: antibiotics, river pollution, sulfachloropyridazine, ecological risk assessment, water quality, sulfonamides, livestock farming, urban sewage, attenuation coefficient, China, environmental monitoring, pollution hotspots