Inflammatory bowel disease and related chronic gastrointestinal disorders remain difficult to model in conventional species because human disease involves a complex interaction among mucosal immunity, microbiome dysbiosis, epithelial barrier dysfunction, genetics, infectious triggers, and psychosocial stress. For global biopharmaceutical companies developing anti-inflammatory biologics, microbiome therapies, barrier-protective agents, or gut-targeted immunomodulators, a clinically relevant NHP IBD model can provide important translational value before entering human trials.
The 2026 review by Bacon, Lawhon, Gray, and Hodo, titled "A review of chronic enterocolitis of rhesus macaques (Macaca mulatta) and potential as a naturally occurring model for post-infectious irritable bowel syndrome," published in Frontiers in Veterinary Science, evaluates chronic enterocolitis (CE) in rhesus macaques as a naturally occurring gastrointestinal disease model. Although the article focuses on CE and post-infectious irritable bowel syndrome (PI-IBS), many pathological features overlap with IBD-related research needs, including chronic diarrhea, colonic inflammation, immune-cell infiltration, microbiome disruption, and epithelial injury. The paper was published in Volume 13, 2026, DOI: 10.3389/fvets.2026.1759338.
Core Literature Analysis
Model Establishment
Chronic enterocolitis is described as a major disease burden in colony-housed rhesus macaques, developing in up to 25% of adults and leading to chronic diarrhea, severe weight loss, nutrient malabsorption, epithelial barrier dysfunction, and, in advanced cases, welfare euthanasia. The syndrome has also been referred to as idiopathic chronic diarrhea, chronic idiopathic colitis, or chronic idiopathic diarrhea.
From a translational modeling perspective, CE is valuable because it arises naturally rather than through chemical induction. Reported clinical features include intermittent or continuous non-bloody diarrhea, dehydration, weight loss, and poor response to conventional supportive therapy. The syndrome is often diagnosed in animals less than 5 years old, although older animals may also be affected.
The article highlights several investigated risk factors relevant to NHP gastrointestinal disease modeling, including diarrhea before weaning, low body weight at weaning, hand-rearing, male sex, repeated housing relocation, low social rank, anxious temperament, and reduced gregariousness. These features support the concept that host stress biology may interact with mucosal inflammation and microbial imbalance.
Key Endpoints
For sponsors designing an NHP IBD-related preclinical efficacy study, the review identifies several endpoint categories that are highly relevant.
Clinical endpoints include stool consistency, diarrhea frequency, body weight change, hydration status, appetite, hospitalization history, and treatment response. Some studies defined CE using criteria such as more than 45 days of diarrhea and/or more than 3 hospitalizations for diarrhea over 6 months, combined with negative enteric pathogen screening.
Histopathology is central to model confirmation. Reported lesions include lymphoplasmacytic colitis, colonic mucosal hyperplasia, crypt abscesses, mucosal neutrophils, mucosal hypertrophy, loss of goblet cells, epithelial attenuation or tufting, increased epithelial lymphocytes, and increased trichomonad-like parasites extending into colonic crypts. The review also discusses increased CD3+ intraepithelial lymphocytes, changes in enteroendocrine cells and enterochromaffin cells, and altered local cytokine expression.
Microbiome and pathogen-related endpoints are equally important. CE has been associated with dysbiosis, reduced beneficial microbial profiles, increased Campylobacter, and reduced Helicobacter macacae. One study cited in the review found 40% of CE animals had Campylobacter spp. and 26% had trichomonads, while only 9% of control animals had Campylobacter spp. in low numbers and 0% had trichomonads at necropsy.
Major Findings
A key conclusion is that CE shares multiple characteristics with human chronic intestinal disease, including persistent diarrhea, mucosal immune activation, dysbiosis, and histologic inflammation. While the review positions CE primarily as a potential naturally occurring PI-IBS model, the overlap with IBD biology makes it valuable for broader NHP gastrointestinal inflammation model development.
The review also emphasizes the possible role of Campylobacter as an initiating or disease-modifying factor. In some outdoor-housed populations, up to 80% of rhesus macaques were colonized with Campylobacter species by 1 month of age, and over 69% of adults and juveniles remained asymptomatic carriers of C. coli and/or C. jejuni. Among infected infants, up to 25% developed Campylobacter-associated diarrhea, and half of those animals later developed CE.
Treatment data further reinforce the complexity of this model. Tylosin therapy improved diarrhea and colonic lesions after 10 days of parenteral treatment, and animals treated for up to 6 weeks maintained normal fecal scores during therapy; however, nearly 40% relapsed within 30 days after treatment stopped. A small study using a 14-day combination of vancomycin, neomycin, and fluconazole showed maintained stool improvement, but the authors noted the need for larger studies. Vaccine-related data are also notable: a hydrogen peroxide-inactivated Campylobacter coli vaccine reduced diarrhea incidence from 9.8% in unvaccinated animals to 1.96% in vaccinated animals, with estimated vaccine efficacy of 83%.
Methodological Limitations and Prisys Practice Supplement
Despite its translational value, CE is not yet a fully standardized NHP IBD model. The review notes inconsistent case definitions across studies, limited prospective validation, variable histologic confirmation, and uncertainty about whether Campylobacter is a causal trigger or a secondary consequence of dysbiosis. Some features also differ from classical PI-IBS, including the presence of neutrophils in CE lesions and an apparent male predisposition in rhesus macaques.
At Prisys Biotech, we address these limitations through an integrated NHP gastrointestinal inflammation platform, supporting study-specific model selection, fecal scoring, body-weight monitoring, clinical chemistry, colonoscopy or biopsy-based sampling where appropriate, histopathology, IHC-based immune-cell profiling, cytokine analysis, microbiome sequencing, and qPCR-based pathogen detection. Our experience with macaque GI disease evaluation enables sponsors to distinguish therapeutic efficacy from spontaneous fluctuation, antimicrobial history, diet effects, and colony-level microbiome variation.
Practical Significance for Drug Development
For IBD drug developers, this review reinforces that NHP gastrointestinal models should not be evaluated by clinical diarrhea alone. Robust translational packages should integrate clinical scoring, endoscopic or tissue-based pathology, mucosal immune readouts, microbiome shifts, pathogen screening, and longitudinal recovery or relapse patterns.
A well-characterized NHP CE or IBD-related model may be particularly useful for evaluating anti-inflammatory biologics, epithelial barrier therapies, microbiome-modulating agents, anti-Campylobacter strategies, probiotics, prebiotics, and host-directed immunotherapies. Because CE reflects a naturally occurring chronic intestinal syndrome, it may complement chemically induced rodent colitis models and provide a bridge between mechanistic discovery and human clinical translation.
To explore how Prisys can support your gastrointestinal inflammation pipeline, contact us for customized consultation on our NHP IBD and Chronic Enterocolitis Preclinical Efficacy Evaluation Service.
References
Bacon RL, Lawhon SD, Gray SB, Hodo CL. A review of chronic enterocolitis of rhesus macaques (Macaca mulatta) and potential as a naturally occurring model for post-infectious irritable bowel syndrome. Frontiers in Veterinary Science. 2026;13:1759338. DOI: 10.3389/fvets.2026.1759338.
Laing ST, Merriam D, Shock BC, Mills S, Spinner A, Reader R, et al. Idiopathic colitis in rhesus macaques is associated with dysbiosis, abundant enterochromaffin cells and altered T-cell cytokine expression. Veterinary Pathology. 2018;55:741–752. DOI: 10.1177/0300985818780449.
Yang S, Liu Y, Yang N, Lan Y, Lan W, Feng J, et al. The gut microbiome and antibiotic resistome of chronic diarrhea rhesus macaques and its similarity to the human gut microbiome. Microbiome. 2022;10:29. DOI: 10.1186/s40168-021-01218-3.
Quintel BK, Prongay K, Lewis AD, Raué H-P, Hendrickson S, Rhoades NS, et al. Vaccine-mediated protection against Campylobacter-associated enteric disease. Science Advances. 2020;6:eaba4511. DOI: 10.1126/sciadv.aba4511.
