The study, led by Jiexia Gao and corresponding author Haifeng Liu of the hospital’s Department of Gastroenterology II, was conducted as a retrospective analysis of pediatric patients who presented with gastrointestinal symptoms and were ultimately found to have infection-related multiple colonic ulcers. The clinical motivation is straightforward: as digestive endoscopy has become more widely used in children, doctors are detecting colonic ulcers at a rising rate, and distinguishing between infectious causes and inflammatory bowel disease early in the workup has become one of the most consequential decisions in pediatric gastroenterology. Getting it wrong in either direction carries serious consequences, because the treatments for the two categories of disease are not merely different but in some cases actively harmful if applied to the wrong patient.

The technical challenge at the heart of the report is that infectious colitis and inflammatory bowel disease can look remarkably similar on endoscopic examination. Colonoscopy in all three children showed varying degrees of multiple colonic ulcers, the kind of finding that in many centers would trigger an immediate workup for ulcerative colitis or Crohn’s disease. The overlapping symptoms compound the difficulty. The main complaints in all three cases were abdominal pain and hematochezia, the passage of fresh blood with the stool, which are classic presenting features of both infection-driven inflammation and chronic immune-mediated bowel disease. Without a deliberate search for pathogens, the infectious origin of the ulcers could easily have been missed, and the children might have been started on immunosuppressive therapy designed to dampen the immune system rather than eliminate a microbe.

The first of the three cases involved Entamoeba histolytica, the single-celled parasite responsible for amoebic dysentery. This protozoan invades the lining of the colon and can produce deep, flask-shaped ulcers that bleed and cause cramping pain, an endoscopic appearance that can be mistaken for the continuous mucosal inflammation of ulcerative colitis. Diagnosis typically depends on identifying the organism or its genetic material in stool or tissue samples, and treatment requires specific anti-amoebic drugs rather than the corticosteroids or biologics used for inflammatory bowel disease. The Shanghai team confirmed the pathogen in their patient and documented significant improvement of the ulcers on follow-up after targeted anti-infective treatment, underscoring that a correct microbiological diagnosis converts a potentially chronic, relapsing condition into a curable one.

The second case was caused by Epstein-Barr virus, the ubiquitous human herpesvirus best known for causing infectious mononucleosis. Epstein-Barr virus is an increasingly recognized contributor to gastrointestinal disease, and in some patients it establishes a persistent, active infection in the gut that produces ulceration of the intestinal mucosa. The authors of the report highlight the importance of Epstein-Barr virus-encoded RNA, known as EBER, a molecular marker that can be detected in tissue biopsies by in situ hybridization and that allows pathologists to identify viral presence directly within ulcer tissue. They also reference chronic active Epstein-Barr virus infection, a severe and potentially life-threatening entity in which the virus persists in an uncontrolled fashion. Distinguishing a self-limited or treatable Epstein-Barr virus-associated colitis from Crohn’s disease, which produces patchy, skip lesions of deep inflammation, is a diagnostic exercise that depends heavily on this kind of molecular pathology rather than on endoscopic appearance alone.

The third case was caused by Salmonella Typhimurium, a serotype of the foodborne bacterium Salmonella enterica. Salmonella infection classically produces acute bacterial colitis with diarrhea, fever, and sometimes bloody stool, and in some patients the inflammation becomes severe enough to generate discrete colonic ulcers visible on colonoscopy. Bacterial culture of stool or tissue is the standard route to confirmation, and appropriate antibiotic therapy or supportive care, guided by the susceptibility of the organism, addresses the root cause. As with the amoeba and the virus, the report documents that once the bacterium was identified and treated, the colonic ulcers improved significantly on follow-up, a trajectory very different from the chronic relapsing course expected in untreated inflammatory bowel disease.

The central conclusion the authors draw is that multiple colonic ulcers in children can indeed be caused by infections, and that timely diagnosis requires the integration of pathogen detection with clinical, endoscopic, and pathological findings, followed by targeted treatment. This multimodal approach is the technical core of the paper. Clinical history provides clues such as travel, diet, sick contacts, and the acuity of symptom onset. Endoscopy defines the distribution and morphology of the lesions. Histopathology of biopsy specimens can reveal features that favor infection, such as certain patterns of inflammation, or that favor chronic immune disease, such as basal plasmacytosis and crypt architectural distortion. Layered on top of all of this is direct microbiological testing, including stool studies, cultures, serology, and molecular assays such as EBER in situ hybridization, which together can pin down a specific culprit organism.

The broader significance of the report lies in what it warns against. Immunosuppressive therapy, the mainstay of treatment for ulcerative colitis and Crohn’s disease, works by blunting the immune response in the gut. If that therapy is given to a child whose ulcers are actually driven by an amoeba, a virus, or a bacterium, the result can be uncontrolled proliferation of the pathogen and worsening disease. The authors emphasize that ruling out infection and clarifying the underlying cause early, before committing a child to a diagnosis of inflammatory bowel disease, is essential to ensure timely and appropriate treatment. Their three cases, each caused by a biologically unrelated microbe spanning a protozoan, a herpesvirus, and an enteric bacterium, illustrate just how wide the infectious differential diagnosis for colonic ulceration can be.

The study also reflects a changing diagnostic landscape in pediatric medicine. The increasing use of digestive endoscopy in children means that colonic ulcers are being found more often, including in patients whose symptoms might once have been managed without a definitive anatomical diagnosis. That greater detection rate raises the stakes for accurate etiological classification, because every endoscopically identified ulcer now demands an explanation. The Shanghai team’s experience suggests that pathogen testing should be treated as a routine and early component of the workup for pediatric colonic ulcers, rather than as a fallback pursued only after immunosuppressive therapy has failed. Their retrospective series, while small, adds to a literature they review showing that infectious mimics of inflammatory bowel disease are neither rare nor exotic.

For clinicians, the practical message is a disciplined diagnostic sequence: when a child presents with abdominal pain, hematochezia, and endoscopic evidence of multiple colonic ulcers, obtain thorough microbiological studies alongside the standard inflammatory bowel disease evaluation, interpret the endoscopic and histological findings in light of the pathogen results, and reserve immune-directed therapy for cases in which infection has been reasonably excluded. For the three children in this report, that discipline paid off in the most concrete way possible. Follow-up after targeted anti-infective treatment showed significant improvement of their ulcers, demonstrating that an accurate early diagnosis can spare young patients both the burden of a chronic disease label and the risks of treatments they never needed.

Subject of Research: Infectious causes of multiple colonic ulcers in children that mimic inflammatory bowel disease

Article Title: Resembling inflammatory bowel disease: infectious causes of multiple colonic ulcers in children—three case reports and a literature review

Article References: Gao, J., Lin, K., Gu, Z., Wang, L., Feng, Y., & Liu, H. (2026). Resembling inflammatory bowel disease: infectious causes of multiple colonic ulcers in children—three case reports and a literature review. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07745-y

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07745-y

Keywords: colonic ulcers, children, inflammatory bowel disease, Entamoeba histolytica, Epstein-Barr virus, Salmonella Typhimurium, colonoscopy, infectious colitis, pediatric gastroenterology, EBER, misdiagnosis, anti-infective treatment

Salmonella Typhimurium is among the leading causes of foodborne gastroenteritis worldwide, and its monophasic variant—distinguished serologically by the absence of one of its two flagellar phases—has surged in prevalence across Europe, the Americas and Asia over recent decades. The lineage, which belongs to sequence type 34 and typically displays the antigenic formula 4,[5],12:i:-, has repeatedly been implicated in outbreaks linked to pork, poultry and processed foods. Yet despite its clear epidemiological importance, the genetic determinants that allowed this clone to outcompete its biphasic ancestor, the previously prevalent ST19 lineage, had remained uncertain. The new study set out to resolve that question at unprecedented scale.

The team’s comparative analysis of tens of thousands of genomes revealed a striking pattern: the expanding ST34 clone carried a frameshift mutation in dinB, the gene encoding a translesion DNA synthesis polymerase also known as DNA polymerase IV. The mutation, a deletion of a single thymine residue within a homopolymeric tract of seven thymidines near the 5′ end of the gene, introduces a premature stop codon that truncates the 39.7-kilodalton DinB protein to a nonfunctional fragment of roughly 1.9 kilodaltons. Because DinB is normally involved in bypassing damaged DNA templates and in generating genetic diversity under stress, its loss initially appears counterintuitive for a pathogen on the rise.

Functional experiments, however, demonstrated that the crippled polymerase has far-reaching downstream consequences. Transcriptomic profiling showed that the frameshift dinB mutation rewires the expression of flagellar genes, altering the balance between the two phase-one and phase-two flagellin systems that Salmonella uses to evade host immune detection. Specifically, the mutation led to transcriptional changes that favored retention of fliC, which encodes phase-one flagellin, and set the stage for the subsequent loss of fljB, the gene encoding phase-two flagellin. Western blot analyses confirmed that dinB-mutant strains displayed an increased proportion of cells expressing FliC, while in vitro motility assays showed that swimming ability was preserved despite the underlying genetic upheaval.

The physiological consequence of this reprogramming became apparent in infection models. Using transposon insertion sequencing and in vivo competition experiments in mice, the researchers found that the requirements for successful gut colonization shifted once fljB was lost. Genes that were dispensable, or even costly, in the ancestral background became essential or advantageous in the mutant context, and vice versa. The frameshift dinB strain carrying the fljB deletion outcompeted the previously prevalent biphasic ST19 lineage in the intestine, indicating that the combination of the polymerase defect and flagellin loss conferred a measurable competitive advantage within the host environment.

To move beyond correlation, the authors built a temporal evolutionary model that simulated the dynamics of four competing lineages: biphasic ST19, biphasic ST34, ST34 carrying the frameshift dinB, and monophasic ST34 carrying both the frameshift and the fljB deletion. The modeling demonstrated that the chronological order of the events matters critically. The dinB mutation had to precede the loss of fljB for the monophasic clone to expand as observed, and the simulated selection coefficients derived from the model were quantitatively consistent with selection estimates computed from real-world changes in genotype frequencies among human clinical isolates. Sensitivity analyses confirmed that the conclusion held regardless of the initial frequency of ST34, the presence or absence of spatial population structure, or the precise metric used to quantify selection.

This ordered dependency is what the researchers describe as a stepwise pathoadaptation model: a sequence of gene-loss events in which each deletion reshapes the genetic background so that the next loss becomes beneficial rather than deleterious. The concept echoes a growing recognition in microbial evolution that genome reduction can be a creative force. Recent work on Vibrio parahaemolyticus, for example, showed that wave succession within a pandemic clone was likewise driven by gene loss, and earlier studies documented how monophasic Salmonella Typhimurium microevolved during a prolonged epidemic in the United Kingdom. The new study, however, is notable for linking the ecological success of a zoonotic lineage to a specific, mechanistically validated chain of molecular events.

The broader implications extend to public health forecasting. If the emergence of major bacterial clones can depend on relatively simple, ordered mutational steps, then surveillance systems that monitor homopolymeric tracts and other mutation-prone loci may gain predictive power over which lineages are poised to expand. The study’s data resources—including genomic data deposited at the China National GeneBank Database, Enterobase and NCBI, transcriptomic data under accession GSE280131, proteomic data via PRIDE, and transposon-sequencing reads under BioProject PRJNA1347559—provide a substantial foundation for such efforts. The mathematical model code has also been made publicly available on GitHub, enabling other groups to test the generality of the sequential gene-loss framework in other pathogens.

At the same time, the work underscores how little of bacterial adaptation is driven by gene acquisition alone. Monophasic ST34 also carries traits such as copper resistance and heavy-metal tolerance that have been implicated in its persistence in livestock production environments, and antimicrobial resistance remains a defining feature of many circulating clones. But the new analysis places gene loss at the center of the lineage’s rise, reframing flagellar phase variation—a long-studied quirk of Salmonella biology—as a decisive axis of clonal competition. As the authors note, understanding the genetic factors facilitating the emergence of infectious diseases is critical, and this study delivers a concrete mechanistic answer for one of the most consequential zoonotic pathogens of the modern food system. The lesson is uncomfortable but clarifying: for bacteria, sometimes less is more, and the road to pandemic status can be paved by the genes a pathogen leaves behind.

Subject of Research: Stepwise gene loss driving the clonal expansion of monophasic Salmonella Typhimurium ST34

Article Title: Sequential gene loss promotes expansion of monophasic Salmonella Typhimurium ST34

Article References: Wu, X., Wang, T., Jia, C., Zhou, H., Li, Y., Baker, S., & Yue, M. (2026). Sequential gene loss promotes expansion of monophasic Salmonella Typhimurium ST34. Nature Microbiology. https://doi.org/10.1038/s41564-026-02483-4

Image Credits: AI Generated

DOI: 10.1038/s41564-026-02483-4

Keywords: Salmonella Typhimurium, monophasic ST34, gene loss, dinB, flagellin, fljB, pathoadaptation, bacterial evolution, genomic epidemiology, foodborne pathogen, zoonotic disease, Nature Microbiology