BACKGROUND:Fecal microbiota transplantation (FMT) has emerged as a key tool to explore the role of the microbiome-gut-brain axis in psychiatric disorders. However, the field is hindered by significant methodological inconsistencies. METHODS:A comprehensive literature search identified 31 studies performing FMT from human patients with psychiatric conditions into rodent models. RESULTS:None of the 31 studies followed an identical FMT protocol. Significant heterogeneity was observed across studies in rodent model selection, including germ-free, antibiotic-pretreated, or specific pathogen-free approaches, in antibiotic regimens, timing and microbiota depletion verification, as well as in FMT donor strategy, dosage, frequency, engraftment assessment, and behavioral testing schedules. CONCLUSIONS:This review highlights the necessity for standardized methodologies in microbiome research. Evidence-based recommendations are provided to promote reproducibility in future work. Investigators are encouraged to publish transparent and rigorous protocols, to enhance the translational potential of microbiome-gut-brain axis research.

TL1A and its receptor DR3 are key regulators of mucosal immune responses, but their role in periodontal disease is unknown. Herein, we investigated whether TL1A/DR3 signaling contributes to mucosal immune amplification and tissue-destructive inflammation in periodontitis using SAMP1/YitFc (SAMP) mice, which develop spontaneous ileitis and periodontal disease. DR3 deficiency markedly attenuated alveolar bone loss and improved periodontal architecture, restoring a phenotype comparable to healthy AKR (parental) controls. Gingival tissues from wild-type SAMP mice exhibited increased expression of both Tnfsf15 (encoding TL1A) and Tnfrsf25 (encoding DR3), with both positively correlating with disease severity. This was accompanied by elevated levels of IL-17, TNF-α, and IL-1β, and by increased numbers of CD4+ T helper cells and neutrophils. Conversely, SAMPxDR3-/- mice exhibited reduced inflammatory cytokine production and immune cell accumulation. These findings support a model in which the TL1A/DR3 axis is associated with amplification of mucosal immune responses in periodontal disease, linking effector T cell activation, increased cytokine production, and recruitment of innate immune cells. Altogether, our data identify the TL1A/DR3 cytokine-receptor pair as a potential regulator of inflammatory circuits that drive periodontal pathology. Blocking this pathway may provide a therapeutic modality for patients affected by chronic periodontitis.

Despite advances in immunosuppressive therapies, treatment-refractory inflammatory bowel disease (IBD) remains a major challenge. An annual loss of response occurs in 10–20% of patients receiving advanced therapies, and only 30–50% achieve clinical remission. This therapeutic ceiling highlights the necessity to explore novel therapy. At the same time, the use of complementary and alternative medicine (CAM) is prevalent in this population. Among these, Indigo Naturalis (IN), a traditional herbal supplement, has shown promise for inducing clinical response in ulcerative colitis (UC), a subtype of IBD. The objective of this pilot study is to examine the efficacy of IN in treating UC patients refractory to advanced therapy and explore potential cytokine pathways involved. We conducted a retrospective chart review of UC patients treated with IN at an academic center between 1/1/2023 and 5/1/2025. Demographics, disease phenotype, concomitant medications, prior advanced therapies, and IN dosing were abstracted from the medical records. Clinical response and remission were defined by standard criteria for the partial Mayo score (pMayo). Adverse events were documented. Cytokine analysis was performed on plasma using a commercial Proteome Human Cytokine Array kit. 11 UC patients were started on IN (mean age 53.4 ± 16.7 years; 36% female). 9 patients had failed at least one advanced therapy, with 55% having been on 3 or more advanced therapies (Table 1). The median baseline pMayo was 5 with IQR 3. The IN dose ranges from 1-3 grams daily. 36% of patients took IN for over a year. Following IN initiation, either as monotherapy or adjunctive therapy, 8 of 11 patients (72.7%) achieved a clinical remission. 1 patient discontinued IN due to worsening abdominal pain, while 2 patients discontinued IN due to lack of benefit. Cytokine analysis was performed in 2 UC controls and 2 UC patients taking IN. Patients on IN had decreased signal intensity for both complement C5/C5a and CXCL11/I-TAC compared to controls. The majority of patients with treatment-refractory UC experienced clinical improvement with IN, and treatment was well tolerated. These findings suggest that IN may represent a promising adjunctive therapy in refractory disease and warrant further investigation in larger clinical trials with mechanistic endpoints.

The presence of extraintestinal manifestations with cutaneous diseases in patients with inflammatory bowel disease (IBD) can pose significant complications. Though the prevalence of IBD has been increasing in racial and ethnic minority groups, most literature has characterized several cutaneous manifestations (CM) of IBD in patients of white skin, with a lack of studies describing these complications in patients with other skin tones. Our study aimed to determine the rates of various CM of IBD in skin of color using a health care database to identify white and non-white patients with a diagnosis of IBD who were prescribed at least one IBD-specific medication or advanced therapy. Of the total IBD patients, after propensity score matching there were 35,624 patients identified in both the white and non-white cohorts. Among non-white patients, there was a >2-fold odds of developing hidradenitis suppurativa and increased odds of vitiligo. Psoriasis, herpes zoster, and leukocytoclastic vasculitis exhibited a decreased association in non-white patients. There was no difference in erythema nodosum, pyoderma gangrenosum, oral aphthae, Sweet syndrome, and acquired epidermolysis bullosa. With the rise of IBD in non-white populations, the representation of CM of IBD in this population is significantly limited, underrecognized, and thus undertreated. Our results reveal increased prevalence of several CM in the non-white IBD patient population. Recognition of CM in non-white patients with IBD can enhance quality of life and reduce morbidity among this population.

Chronic colitis in patients with ulcerative colitis (UC) and Crohn’s disease (CD) predisposes patients to debilitating symptoms and an increased risk of colorectal cancer (CRC). Despite advances in biologics, only 30–40% of patients achieve sustained remission, underscoring the need for novel agents with complementary mechanisms of action and reduced toxicity. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist originally developed for type 2 diabetes, has demonstrated favorable metabolic and anti-inflammatory effects, suggesting potential utility in gastrointestinal disease. While GLP-1 receptor agonists have shown promise in acute colitis models and epidemiological studies indicate reduced CRC incidence among exposed individuals, the effects of dual agonists in chronic colitis-associated cancer (CAC) remain unknown. We evaluated Tirzepatide in the Winnie mouse, a model of spontaneous UC-like colitis and CAC. Weekly administration of Tirzepatide (30 nmol/kg, 8 weeks) markedly reduced colitis severity and tumor burden compared to vehicle controls. Treated mice exhibited improved weight stability independent of obesity, reflecting attenuation of inflammation and tumorigenesis rather than metabolic effects. Histologic analyses confirmed reduced inflammatory scores, preservation of crypt architecture, and fewer dysplastic lesions. At the molecular level, Tirzepatide suppressed transcription of colon cancer-associated genes (Axin2, Myc, Cdkn1a, Lgr5) and reduced pro-survival and proliferative signaling proteins (p-AKT, p-PFK2, Cyclin D1). Inflammatory cytokine transcripts (Il6, Il1β, Tnf) and stool lipocalin-2 levels were significantly decreased, corroborating broad anti-inflammatory activity. These findings align with reports of Tirzepatide suppressing tumor growth in patient-derived CRC xenografts, reinforcing a potential direct effect on epithelial oncogenic pathways rather than an indirect consequence of weight loss. Our results support Tirzepatide as a promising therapeutic candidate that bridges metabolic and immune pathways to mitigate colitis and CAC. Its dual receptor activity may synergize with existing therapies such as mesalamine or biologics, offering an advanced combination therapeutic approach to IBD management and cancer prevention. Future studies are warranted to define dosing strategies that dissociate metabolic from anti-inflammatory effects and to evaluate long-term outcomes in translational and clinical settings.

Crohn’s disease (CD) is a chronic gastrointestinal disorder involving host genetics, environment, and gut microbiota, with microbial-based approaches holding high therapeutic potential. This study focused on the potential of Lactobacillus plantarum to attenuate intestinal inflammation in SAMP1/YitFc mouse models of colitis and ileitis. We tested the potential of L. plantarum to; (i) protect against the severity of dextran sodium sulfate (DSS)-induced colitis (acute flare model), (ii) prolong Dexamethasone (DEX)-induced remission in older SAMP mice with established ileitis (remission model), (iii) prevent/attenuate disease onset in young SAMP mice (preclinical model). Body weight, fecal myeloperoxidase (fMPO), gut permeability (fluorescein isothiocyanate (FITC)-dextran), colonoscopy, 3-D stereomicroscopy and histology of intestinal tissues were assessed. Administration of L. plantarum (Lac) significantly attenuated intestinal inflammation across multiple SAMP mouse models. In DSS-induced colitis, treatment improved clinical and histologic disease activity, evidenced by greater weight retention, preserved colon length, enhanced barrier integrity, and reduced fMPO and colonoscopy scores (Lac: 3.1 ± 0.8 vs. control: 5.3 ± 1.2, p = 0.02). In DEX-induced remission model, L. plantarum prolonged remission and reduced relapse severity, demonstrated by improved weight maintenance, decreased gut permeability and inflammatory burden, and lower histologic scores (Lac: 6.0 ± 2.1 vs. control; 9.6 ± 2.0, p = 0.03). Early-life intervention further mitigated spontaneous ileitis, with reductions in intestinal permeability, inflammatory activity, and macroscopic lesion severity (Lac: 0.6 ± 0.7 vs. control: 1.9 ± 0.6, p = 0.03). L. plantarum improved gut barrier integrity and attenuated intestinal inflammation in experimental colitis and chronic ileitis models of IBD.

BACKGROUND:Inflammatory bowel disease (IBD) is a multisystem illness with intestinal and extraintestinal manifestations. We aimed to analyze the association of developing pulmonary diseases (PDs) in patients with IBD. METHODS:In this retrospective cohort study, TriNetX was used to identify patients with IBD who were prescribed at least one IBD-specific medication or advanced therapy. Patients with an inpatient visit and no IBD comprised the control group. Propensity score matching (PSM) was used to balance cohorts. The odds ratio (OR) of developing PDs all-cause mortality were determined. RESULTS:After PSM, there were 155,668 patients (46.6±17.5 y, 50.9% female) in each group. Patients with IBD had an increased prevalence of developing all assessed PDs except for pyothorax (P=0.087), lung abscesses (P=0.411), pleural disease (OR: 0.89 [0.80-0.98], P=0.013), and pneumothorax (OR: 0.67 [0.62-0.73], P<0.001) compared with the control group. There were at least 2-fold increased prevalence of developing asthma (OR: 2.17 [2.09-2.26]), bronchiectasis (OR: 2.35 [2.12-2.61]), chronic bronchitis (OR: 2.40 [2.11-2.72]), and vasculitis (OR: 2.33 [1.99-2.72]) compared with the control group (all P<0.001). CONCLUSION:Given the increased association of developing PDs, clinicians should engage in proactive monitoring and risk reduction strategies to mitigate the development of various PDs in the IBD patient population.

Gut dysbiosis and neural inflammation occur in patients with amyotrophic lateral sclerosis (ALS), including those with a causal mutation in chromosome 9 open reading frame 72 (C9ORF72). How gut commensals interact with common ALS genotypes to impart risk of neural degeneration remains unclear. Here, we identify 10 phylogenetically diverse bacterial strains that promote cytokine release in a C9orf72-dependent manner. Metatranscriptomics implicated the glycogen biosynthesis pathway as a driver of inflammation. Colonization of germ-free C9orf72-deficient mice with Parabacteroides merdae that produced inflammatory glycogen enhanced monocytosis, blood-brain barrier breakdown, and T cell infiltration into the central nervous system. Enzymatic digestion of glycogen in the gut promoted survival of C9orf72-deficient mice and dampened microglial reactivity in the brain. A survey of human fecal samples demonstrated that inflammatory forms of glycogen were present in gut contents from 15/22 patients with ALS, 1/1 patient with C9ORF72 frontotemporal dementia (FTD), and 4/12 healthy controls. Together, the results of this work identify bacterial glycogen as a modifiable mediator of immune homeostasis in the gut and brain.