The research team, led by Fatemeh Shayesteh and colleagues at Shahrekord University of Medical Sciences in Iran, set out to test whether these two probiotic strains could modulate inflammasome signalling, a pathway increasingly implicated in chronic mucosal inflammation across species. Inflammasomes are cytosolic protein complexes that act as intracellular alarm systems, sensing microbial or endogenous danger signals and activating the enzyme caspase-1. Once activated, caspase-1 cleaves and matures the potent inflammatory cytokines interleukin-1β and interleukin-18, which drive neutrophil recruitment, tissue damage, and the self-perpetuating cycle of inflammation characteristic of colitis. When the NLRP3 inflammasome becomes overactive, as has been documented in both human and veterinary cases of inflammatory bowel disease, the result is persistent mucosal injury and poor healing.

To model the disease, the researchers induced ulcerative colitis in 40 male Wistar rats by administering a single intrarectal dose of 4% acetic acid under anaesthesia, a well-established chemical method that reproduces key histopathological features seen in naturally occurring colitis of dogs, cats, and cattle, including mucosal ulceration, epithelial barrier dysfunction, and infiltration of inflammatory cells. The animals were randomly divided into five groups of eight: a healthy control group receiving saline, an untreated colitis group, a group treated with the standard anti-inflammatory drug mesalazine at 300 mg/kg per day, and two probiotic groups receiving daily oral gavage of either B. coagulans or L. acidophilus at a concentration of 10⁹ colony-forming units per millilitre for seven consecutive days. On day ten, the rats were euthanized and colonic tissues were collected for molecular, biochemical, and histological analysis.

The molecular results were striking. Compared with healthy controls, colitis induction caused dramatic upregulation of inflammasome-related genes in colonic tissue: interleukin-18 expression rose roughly 7.6-fold, NLRP3 about 11-fold, caspase-1 more than 12-fold, and tumour necrosis factor-alpha more than 6-fold. Treatment with either probiotic strain significantly reversed these changes. In the L. acidophilus group, expression of all four genes fell substantially relative to untreated colitis animals, and B. coagulans produced reductions of similar magnitude. Notably, the probiotic effects were comparable to those achieved with mesalazine, the benchmark therapy, which itself suppressed the same gene set. The convergence of probiotic and pharmacological outcomes at the transcript level suggests that these bacteria engage the same inflammatory circuitry that conventional drugs target, but through biological mechanisms rather than chemical inhibition.

Protein-level measurements reinforced the gene expression data. Using enzyme-linked immunosorbent assays on colonic tissue homogenates, the team found that colitis induction caused enormous increases in interleukin-1β and interleukin-17 protein concentrations. Both probiotics significantly lowered these cytokines, again paralleling the effect of mesalazine. Interleukin-1β is the direct downstream product of caspase-1 activation within the inflammasome, so its reduction provides functional confirmation that probiotic treatment genuinely dampens inflammasome output rather than merely altering gene transcription. Interleukin-17, meanwhile, is a signature cytokine of the Th17 immune axis that drives neutrophil recruitment and barrier disruption, meaning the probiotics appeared to suppress inflammation at multiple points along the pathological cascade.

The structural evidence was equally persuasive. Macroscopic examination of the colons, scored independently by two blinded observers using the Wallace and Keenan system, revealed severe ulceration, hyperaemia, inflammation, and oedema in untreated colitis animals, with a mean wound score of 3.25. Both probiotic groups showed marked improvement, with L. acidophilus achieving a mean score of 1.50, identical to the mesalazine group, and B. coagulans scoring 1.83. Colon length and weight, which serve as indirect measures of tissue oedema and shortening, were significantly restored in both probiotic groups compared with the untreated colitis group, indicating that the bacteria helped preserve gross tissue morphology.

Under the microscope, the differences were just as clear. Haematoxylin and eosin stained sections from untreated colitis rats displayed pronounced thickening of the mucosal, submucosal, and muscularis layers, extensive epithelial cell loss, a marked reduction in goblet cells, severe leukocyte infiltration, and lymphoid hyperplasia across all tissue layers. In contrast, sections from probiotic-treated animals showed reduced layer thickness, fewer inflammatory cells, milder crypt damage, and tissue involvement confined to the 1 to 25% range, compared with 51 to 75% in the colitis group. Histopathological scores fell from 4 in the colitis group to 2 in both probiotic groups, matching the mesalazine-treated animals. The restoration of goblet cells, which produce the protective mucus layer lining the gut, points to genuine epithelial repair rather than simple suppression of visible inflammation.

The mechanistic story behind these findings is likely multifaceted. Probiotics are known to reinforce epithelial integrity, compete with pathogenic bacteria for adhesion sites and nutrients, produce antimicrobial compounds, and regulate immune cell activity through Toll-like receptor pathways and the production of short-chain fatty acids. The authors suggest that suppression of inflammasome signalling may occur indirectly through these routes: by modulating Toll-like receptor activation, probiotics can shift the danger-sensing environment of the gut mucosa away from the chronic alarm state that keeps NLRP3 primed. Each strain also brings distinct practical advantages. B. coagulans is a spore-forming lactic acid bacterium whose resilient spores survive harsh storage conditions and the acidic gauntlet of the gastrointestinal tract, a trait particularly valuable in farm settings. L. acidophilus, by contrast, is a strong colonizer of the intestinal tract with well-documented immunomodulatory properties, making it well suited to companion animals with chronic enteropathies.

The veterinary implications extend well beyond the laboratory. Chronic inflammatory gut diseases reduce productivity in livestock, impair growth in young animals, and increase morbidity in pets, while long-term drug therapy raises concerns about cost, side effects, and, in food animals, drug residues in the food supply. Probiotics that measurably reduce inflammasome activation and pro-inflammatory cytokines could serve as adjuncts that allow lower doses of conventional drugs, or as standalone interventions in milder cases. The study also fits into a broader trend in veterinary microbiology toward multi-strain formulations, since combinations of Bacillus and Lactobacillus species are thought to target different aspects of gut ecology and immune regulation simultaneously, potentially offering synergistic benefits over single-strain products.

Important caveats remain. Some inflammation and leukocyte infiltration persisted even in probiotic-treated animals, indicating that these bacteria alleviate disease severity but may not fully replace pharmacological therapy in severe cases. Moreover, the murine model, while translational, differs from dogs, cats, and livestock in microbiota composition and immune function, so clinical trials in target veterinary species are the necessary next step, along with optimization of dosing regimens and formulation of multi-strain products tailored to different animal populations. Still, by connecting a practical, shelf-stable probiotic pair to a specific molecular pathway central to colitis pathology, the study provides a mechanistic bridge between the empirical use of probiotics in animal health and the modern immunology of inflammatory disease, and it does so with the kind of rigorous, multi-level evidence, from gene expression to protein to tissue architecture, that could finally move veterinary probiotics from folklore to pharmacology.

Subject of Research: Probiotic modulation of NLRP3 inflammasome signalling in experimental ulcerative colitis

Article Title: Probiotic Intervention With Bacillus coagulans and Lactobacillus acidophilus in Small Animals Experimental Ulcerative Colitis: Insights From a Small Animal Model

Article References: Shayesteh, F., Shahini Shams Abadi, M., Rouhi, L., Doosti, A., & Bagheri, N. (2026). Probiotic Intervention With Bacillus coagulans and Lactobacillus acidophilus in Small Animals Experimental Ulcerative Colitis: Insights From a Small Animal Model. Veterinary Medicine and Science, 12(6), Article e70883. https://doi.org/10.1002/vms3.70883

Image Credits: AI Generated

DOI: 10.1002/vms3.70883

Keywords: probiotics, Bacillus coagulans, Lactobacillus acidophilus, ulcerative colitis, NLRP3 inflammasome, veterinary medicine, inflammatory bowel disease, interleukin-1beta, mesalazine, rat model, gut microbiota, cytokines

Mesalazine, also known as 5-aminosalicylic acid or 5-ASA, has been a cornerstone of inflammatory bowel disease management for decades. It is prescribed to both quell active flares of ulcerative colitis and Crohn’s disease and to keep those diseases in remission over the long term. Because it is generally well tolerated, patients often take it for years with little thought. Yet the new report underscores that even this familiar molecule can provoke serious lung injury. Drug-induced eosinophilic pneumonia occurs when an offending medication triggers an influx of eosinophils into the alveolar air spaces and the interstitial tissue of the lungs, impairing oxygen exchange and producing cough, breathlessness, and infiltrates visible on chest imaging. Diagnosis typically rests on a compatible drug history, elevated eosinophils in peripheral blood or bronchoalveolar lavage fluid, characteristic imaging, and exclusion of infection and other causes.

What makes this case exceptional is timing. In the vast majority of reported instances, mesalazine-related lung injury emerges two to six months after treatment begins, a lag that can easily lull clinicians into overlooking the drug as a culprit. The literature contains only a handful of cases in which symptoms appeared within ten days of the first dose, and the present patient, whose cough began on day seven, now ranks among the earliest ever recorded. By the time she was referred to hospital on day 39, chest radiography showed worsening consolidation in the right upper lung field along with a pleural effusion. Computed tomography demonstrated diffuse consolidation concentrated in the right upper lobe. Her vital signs remained stable, with an oxygen saturation of 96 percent on room air, but her white cell differential told a striking story: eosinophils made up 37.8 percent of a total count of 9,700 cells per microliter, and her C-reactive protein was mildly elevated at 2.67 mg/dL.

To pin down the diagnosis, clinicians turned to bronchoscopy. Bronchoalveolar lavage returned fluid with a total cell count of 5.88 × 10⁶ per milliliter, of which an extraordinary 78.6 percent were eosinophils, a signature finding in eosinophilic lung disease. Transbronchial biopsy and transbronchial lung cryobiopsy, a technique that freezes a larger sample of lung tissue for histological analysis, revealed dense eosinophilic infiltration in both the alveolar spaces and the interstitium. Bacterial and mycobacterial cultures and cytology were all negative, ruling out infection and malignancy. With the drug withdrawn, the clinical course became its own confirmation: chest radiography began improving just two days after mesalazine was stopped, the patient’s cough resolved within a month, and pulmonary infiltrates and peripheral eosinophilia had normalized six weeks later, all without corticosteroid therapy. She was subsequently transitioned to vedolizumab, a gut-selective biologic, for her ulcerative colitis, and the pneumonia did not recur.

Behind this single patient stands a much larger body of evidence assembled by the reporting team. Searching MEDLINE and screening references from prior reviews, the authors identified 57 additional cases of mesalazine-induced lung injury, bringing the total analyzed to 58. The demographic picture is instructive: patients ranged from 14 to 84 years of age, with a median of 35 and a peak in the third decade of life, and women outnumbered men 34 to 24. Ulcerative colitis accounted for 84 percent of underlying diagnoses, with Crohn’s disease making up most of the remainder. Eosinophilic pneumonia was the most common pattern of injury, representing 43 percent of cases, followed by interstitial pneumonia at 27 percent and organizing pneumonia at 10 percent. Most patients, 67 percent, showed bilateral infiltrates, though unilateral disease, as in this case, does occur and can mislead clinicians toward an infectious diagnosis.

The timing data from that literature review are perhaps the most clinically valuable takeaway. While lung injury typically develops two to six weeks after initiation, roughly 10 percent of cases occur within the first two weeks, and only two cases on record, including this one, manifested within ten days. In a focused analysis of 18 well-documented eosinophilic pneumonia cases, symptom onset ranged from seven days to fourteen months, with 70 percent occurring within two months. The median cumulative dose at onset was 81 grams of mesalazine; the present patient had consumed only about 14 grams when her symptoms began. That discrepancy carries real mechanistic weight, because a reaction that ignores both the duration of exposure and the total dose ingested is the hallmark of hypersensitivity rather than toxicity.

That mechanistic distinction matters for how clinicians think about drug safety. Drug-induced lung injury generally arises through two principal pathways: direct cytotoxic damage to alveolar epithelial or endothelial cells, which tends to be dose-related, and immune-mediated inflammation, which can erupt unpredictably at any exposure level. The evidence points firmly toward the immune pathway for mesalazine. Researchers propose that the drug may skew immune signaling toward a Th2-dominant response, in which cytokines such as interleukin-5 drive the production, recruitment, and activation of eosinophils, ultimately seeding them in lung tissue. Pharmacokinetic data reinforce the plausibility of a hypersensitivity mechanism: approximately 20 to 30 percent of orally administered mesalazine and about 10 percent of rectal formulations are absorbed systemically, and eosinophilic pneumonia has been reported even after rectal administration, indicating that small systemic exposures can suffice to ignite the reaction.

The case also settles a long-standing question about the older drug sulfasalazine, a prodrug that is metabolized in the gut into mesalazine and sulfapyridine. When eosinophilic pneumonia occurred in patients taking sulfasalazine, toxicity was often attributed to the sulfapyridine moiety. But the accumulating reports of identical lung injury with mesalazine alone suggest that the 5-aminosalicylic acid molecule itself is capable of triggering the immune response. For the millions of patients with inflammatory bowel disease who take 5-ASA compounds worldwide, this reframing means that no formulation of the drug class can be considered free of pulmonary hypersensitivity risk, however rare that risk may be in absolute terms.

One intriguing wrinkle in the present case is the patient’s respiratory history. She had suspected bronchial asthma and used inhaled corticosteroids as needed, and her fractional exhaled nitric oxide, a noninvasive marker of eosinophilic airway inflammation, was elevated at 51 parts per billion. The authors caution that this reading may have reflected pre-existing asthmatic airway inflammation rather than pneumonia alone, and they note that only one previously reported mesalazine lung-injury patient had a history of bronchial asthma. Whether underlying allergic airway disease can accelerate the onset of drug-induced eosinophilic pneumonia remains uncertain, but the possibility offers a concrete hypothesis for future research and a reason for heightened vigilance in asthmatic patients starting the drug.

The practical message for clinicians and patients alike is one of awareness rather than alarm. Corticosteroids, the usual mainstay of eosinophilic pneumonia treatment, are not always necessary; simple drug withdrawal can be sufficient when respiratory status is stable, as this case demonstrates. Yet some patients have received prednisolone out of concern that stopping mesalazine might precipitate a relapse of their inflammatory bowel disease, illustrating the delicate balancing act physicians face. The authors’ conclusion is straightforward: eosinophilic pneumonia can develop early in the treatment course, and drug-induced lung injury should be considered whenever respiratory symptoms or pulmonary infiltrates appear during mesalazine therapy. For a drug taken daily by so many, recognizing that the lungs can protest within a single week of the first tablet may make the difference between a swift, uncomplicated recovery and a prolonged diagnostic odyssey.

Subject of Research: Rapid-onset mesalazine-induced eosinophilic pneumonia occurring seven days after drug initiation

Article Title: Rapid Onset of Mesalazine‐Induced Eosinophilic Pneumonia Manifesting 7 Days After Initiation: A Case Report

Article References: Inazaki, T., Takeda, K., Iwasaki, M., Tajima, H., Shionoya, Y., Hirama, R., Sato, S., Naito, A., Kawasaki, T., Ikari, J., Kageyama, S., Ikeda, J.-I., & Suzuki, T. (2026). Rapid Onset of Mesalazine‐Induced Eosinophilic Pneumonia Manifesting 7 Days After Initiation: A Case Report. Respirology Case Reports, 14(9), Article e70758. https://doi.org/10.1002/rcr2.70758

Image Credits: AI Generated

DOI: 10.1002/rcr2.70758

Keywords: mesalazine, eosinophilic pneumonia, ulcerative colitis, drug-induced lung injury, inflammatory bowel disease, bronchoalveolar lavage, hypersensitivity pneumonitis, 5-aminosalicylic acid, adverse drug reaction, respirology, eosinophils, case report