Introduction

The cause of Crohn’s Disease (CD) remains unclear; however evidence suggests that dietary factors play a key role. With a rising incidence and no definitive cure, identifying modifiable risk factors is critical in preventing CD development. We aimed to study the association between fermentable dietary fibre intake and the future development of CD in an at-risk population.

Aims & Methods

Participants were recruited as part of the Crohn’s and Colitis Canada GEM study, a prospective cohort study of healthy first-degree relatives of patients with CD. At enrolment, a validated food frequency questionnaire was administered. Pectin, β-glucan, inulin, fructooligosaccharides (FOS), and arabinoxylan intake were quantified, and values energy-adjusted. Survival analysis was used to test the association between intake of fibre subtypes and risk of CD development. Generalized estimating equation tested the association between fibre intake and baseline impaired intestinal permeability (fractional urinary excretion of lactulose to mannitol ratio (LMR) >0.025); subclinical gut inflammation (faecal calprotectin (FCP) >250 μg/g); and faecal microbiome composition via 16s rRNA sequencing.

Results

76 of the 2,659 participants developed CD with a median follow-up of 8.9 years (IQR=5.7-12.3). Median age at recruitment was 17 years (IQR=12-25). 47% were male. Higher intake of inulin (HR = 0.78; 95% CI=0.61–0.99; p=0.04) and β-glucan (HR = 0.78; 95% CI=0.61–0.99; p=0.04) were associated with a reduced risk of CD development. No fibre subtype was associated with a higher risk of CD development. Lower intake of pectin, inulin, FOS and β-glucan was associated with impaired intestinal permeability (0.005<p<0.04). Lower inulin intake was associated with high FCP levels (p = 0.046). Higher pectin intake was associated with increased alpha diversity of faecal microbiome (p = 0.028). Higher inulin, FOS and pectin intake was associated with a shift in microbial taxa previously shown to be protective against CD onset in the GEM cohort; a reduction in Ruminococcus torques and an increase in NK4A214 group (phylum Firmicutes) presence (3.25×10⁻¹⁰<q<0.04).

Conclusion

This study demonstrates that dietary intake of fermentable fibre subtypes is associated with a reduced risk of CD development as well as with pleiotropic changes in CD risk biomarkers including microbiome, intestinal permeability, and subclinical inflammation. This suggests that the potential benefit of fermentable fibres on CD risk may involve changes in barrier function, and microbiome composition and function. Targeted interventions based on these findings could prove effective in preventing the onset of CD.

Introduction

Microplastic particles (MPs), defined as plastic fragments smaller than 5 mm, are pervasive pollutants that accumulate in ecosystems and the human food chain (1). Literature points at various health risks, including the induction of carcinogenesis (2). Emerging evidence from animal models (3) suggests that MPs may influence the gut microbiome, but the impact on the human gut microbiome remains poorly understood.

Aims & Methods

This study aimed to evaluate how various MP types influence gut microbial composition and metabolism using an ex vivo bioreactor model, with a focus on exploring potential carcinogenic effects arising from MP–microbiome interactions.
Stool samples from healthy donors were used to inoculate bioreactor cultures, which were maintained under anaerobic conditions for five days with daily nutrient feeding. These cultures were exposed to five common MP types—polystyrene (PS), polypropylene (PP), low-density polyethylene (LDPE), poly(methyl methacrylate) (PMMA), and polyethylene terephthalate (PET)—at concentrations mimicking both estimated human exposure (4) and higher doses to assess dose-dependence. Cell viability and total bacterial counts, as well as culture pH, were measured throughout the experiment. To further explore potential microbiome and metabolic alterations, 16S rRNA gene sequencing and targeted metabolomics were performed.

Results

MP exposure did not lead to significant changes in total or viable bacterial cell counts. However, MP-treated cultures exhibited a consistent and significant decrease in pH compared to controls, suggesting changes in microbial metabolic activity. Microbiome sequencing revealed plastic-type-dependent alterations in microbial composition, with certain bacterial taxa increasing or decreasing in abundance depending on the MP type. These shifts occurred across multiple genera within diverse families, including Lachnospiraceae, Oscillospiraceae, Enterobacteriaceae, and Ruminococcaceae, with the majority of changes occurring withing the phylum Bacillota. These compositional changes were accompanied by shifts in the metabolomic profiles, some of which correlated with the observed pH changes. Several plastic types induced changes in valeric acid levels, while individual MP types were associated with alterations in distinct metabolites such as uracil, lactic acid, and acetic acid.

Conclusion

This study demonstrates that MPs can affect gut microbial activity and metabolism without significantly altering overall bacterial abundance in the short term. The variation in microbiome response across plastic types highlights the complexity of MP-microbiome interactions. Changes in faecal pH are known to be associated with various gastrointestinal diseases (5). Interestingly, some of the MP-induced changes in microbial composition resembled patterns linked to diseases such as depression and colorectal cancer. In contrast, other changes showed patterns that differed from those typically associated with conditions like Parkinson’s disease and irritable bowel syndrome, highlighting the complexity of these associations and the dependency on the context. The bioreactor model provided a controlled environment for identifying direct MP-microbiome interactions; however, in humans, additional factors like diet, immune response, and individual microbiome variations play a role in determining long-term effects. Exposure duration may also play a critical role in shaping the extent and nature of microbiome alterations (6), underscoring the need for further research into the effects of chronic MP exposure and associated health risks.

References

(1) Mamun, A. A., Prasetya, T. A. E., Dewi, I. R., & Ahmad, M. (2023). Microplastics in human food chains: Food becoming a threat to health safety. The Science of the total environment, 858(Pt 1), 159834. https://doi.org/10.1016/j.scitotenv.2022.159834
(2) Kumar, R., Manna, C., Padha, S., Verma, A., Sharma, P., Dhar, A., Ghosh, A., & Bhattacharya, P. (2022). Micro(nano)plastics pollution and human health: How plastics can induce carcinogenesis to humans?. Chemosphere, 298, 134267. https://doi.org/10.1016/j.chemosphere.2022.134267
(3) Hirt, N., & Body-Malapel, M. (2020). Immunotoxicity and intestinal effects of nano- and microplastics: a review of the literature. Particle and fibre toxicology, 17(1), 57. https://doi.org/10.1186/s12989-020-00387-7
(4) Senathirajah, K., Attwood, S., Bhagwat, G., Carbery, M., Wilson, S., & Palanisami, T. (2021). Estimation of the mass of microplastics ingested - A pivotal first step towards human health risk assessment. Journal of hazardous materials, 404(Pt B), 124004. https://doi.org/10.1016/j.jhazmat.2020.124004
(5) Yamamura, R., Inoue, K. Y., Nishino, K., & Yamasaki, S. (2023). Intestinal and fecal pH in human health. Frontiers in Microbiomes, 2, 1192316.
(6) Yin, L., Yang, M., Teng, A., Ni, C., Wang, P., & Tang, S. (2025). Unraveling Microplastic Effects on Gut Microbiota across Various Animals Using Machine Learning. ACS nano, 19(1), 369–380. https://doi.org/10.1021/acsnano.4c07885

Introduction

Management of perianal fistulas in Crohn’s disease (CD) is challenging and requires a multidisciplinary approach, combining surgical drainage and biologic therapies, such as infliximab (IFX). Higher IFX trough concentrations have been associated with improved fistula healing rates. The subcutaneous (SC) formulation of IFX achieves 2–3 times higher and more stable trough levels compared to intravenous (IV) formulation. This study hypothesizes that SC IFX could enhance perianal fistula healing rates in CD patients.

Aims & Methods

REMSILAP study is part of the 3TLAP cohort, a French prospective multicenter observational study evaluating optimal therapeutic strategies for achieving clinical and radiological remission of perianal fistulas in CD at 12 months post-surgical drainage. The REMSILAP substudy focuses specifically on patients receiving SC IFX. Patients who received SC IFX after or within six months prior to surgical drainage were included. Baseline was defined as the day of surgical drainage. The primary outcome was the proportion of patients achieving complete clinical remission defined as Perianal Disease Activity Index (PDAI) fistula drainage subscore = 0 associated with PDAI activity restriction subscore <3 and absence of seton, and radiological remission at 12 months. Here, we present preliminary findings from REMSILAP.

Results

Among the 353 patients enrolled in the 3TLAP cohort, 54 were included in REMSILAP. The cohort consisted of 61.1% male patients, with a median age of 36 years and a median disease duration of 4.5 years. Penetrating disease (B3 phenotype) was present in 40.7%, and 33.3% had a history of surgical resection. At baseline, 40.7% of patients had quiescent disease regarding Harvey-Bradshaw index, while 5.6% had severe disease activity. Biologic exposure prior to inclusion was noted in 42.6%. Surgical drainage, with seton placement, was performed in 74.1% of patients. Forty-eight patients (88%) initiated SC IFX treatment after surgical drainage. Of the patients receiving SC IFX, 50% transitioned to SC IFX after less than three IV infusions. Among those on IV IFX at baseline, 20.4% were receiving a 10 mg/kg dose. Forty-three patients (79.6%) received SC IFX in combination with immunomodulators (azathioprine, methotrexate, or 6-mercaptopurine). The median duration of SC IFX treatment was 13.1 months, with treatment maintained for 67.5% of the follow-up period (mean: 19.3 ± 11.3 months). Forty-three patients (79.6%) were treated with a stable dose of 120 mg/14 days and 6 patients (11.1%) had an intensification of SC IFX dosage to 120mg / 7 days. At 12 months, 42 patients were evaluable for clinical outcomes. Complete clinical healing at 12 months was achieved in 11 patients (27.5%) and association of PDAI restriction subscore <3 and drainage subscore = 0 was found in 18 patients (42.9%). Thirteen patients (34.2%) from the 25 patients who had received at least 6 months of SC IFX treatment showed clinical healing at 6 months. Out of the 26 patients treated with at least 12 months of SC IFX treatment, clinical healing was achieved in 16 patients (61.5%) at 12 months. Among the 11 patients with clinical healing at 12 months, 8 (72.2%) were treated with SC IFX treatment following more than three IFX IV infusions. None of the 11 patients with available MRI date showed radiological healing at 12 months.

Conclusion

Subcutaneous infliximab following surgical drainage of Crohn’s disease perianal fistula demonstrates high treatment persistence and promising rates of fistula healing.

Disclosure

This study was funded by Celltrion Healthcare France

Introduction

Chronic low-grade inflammation, known as inflammageing, has been implicated in the pathogenesis of various digestive diseases. However, large-scale systematic evaluations of the association between inflammageing biomarker profiles and digestive system disorders remain scarce. Understanding these associations may have important implications for early detection and intervention strategies.

Aims & Methods

Leveraging the multidimensional data from the UK Biobank, this study aimed to investigate the longitudinal relationships between circulating inflammatory markers and major digestive diseases. A total of 45,475 participants were included, with inflammageing levels calculated as the average of standardized values of four circulating inflammatory markers: TNF, IL1RN, IL18, and IL6.
Digestive disease outcomes were identified from hospital records (HES) and death registries, covering 25 major diagnoses, including gastroesophageal reflux disease (GERD), inflammatory bowel disease (IBD), and non-alcoholic fatty liver disease (NAFLD). Cox proportional hazards models were used to estimate hazard ratios (HRs), adjusting for age, sex, BMI, smoking, and other potential confounders.
In addition, Mendelian randomization (MR) analysis was conducted using GWAS data derived from inflammageing scores to evaluate potential causal effects on digestive outcomes. Mediation and subgroup analyses were performed to explore possible mediating factors.

Results

In the Cox regression analysis, 22 out of 25 digestive outcomes showed significant associations with baseline inflammageing levels (Bonferroni-corrected P < 0.05), with HRs ranging from 1.2 to 2.4.
Mediation analysis identified neutrophil counts and LDL-C as important mediators in these associations, suggesting potential biological pathways linking inflammageing to digestive disease development.

Conclusion

Elevated baseline inflammageing levels were significantly associated with a wide spectrum of digestive system diseases. The findings highlight a potential mechanistic role of systemic inflammation in digestive disease pathogenesis. The use of inflammageing-related biomarkers may aid in early identification of high-risk individuals, offering opportunities for early prevention and targeted interventions.

Introduction

Faecal microbiota transplantation (FMT) has shown promise as treatment in inducing remission in patients with ulcerative colitis (UC), however effectiveness varies (1). Optimizing FMT protocols involving anaerobic stool processing to improve bacterial viability, dual-route administration and donor selection may improve efficacy.

Aims & Methods

Our aim was to evaluate the effectiveness of an optimized FMT protocol using anaerobically prepared stool from pre-selected donors in a randomized controlled multi-centre trial using dual-route administration in patients with mild-to-moderately active UC. A total of 85 patients were randomized to either receive donor FMT (n = 44) or autologous FMT (n = 41) via four weekly FMTs comprising two dual-route administrations, nasoduodenal administration combined with enema, and two single enemas. The study was performed at the Amsterdam University Medical Centre and University Medical Centre Groningen from June 2020 till January 2025. Follow-up time is 12 months and ongoing. Donors were selected based on their microbiota profile, informed by our previous TURN trial (2, 3). The primary outcome was steroid-free clinical remission at week 8 defined as a total adapted Mayo score of ≤2, with a stool frequency subscore of ≤1, a rectal bleeding subscore of 0, and an endoscopic subscore of ≤1. Open-label extension was offered to patients in the autologous FMT group who did not reach clinical remission.

Results

Eighty-five patients were randomized (mean age 43.6 years, 48% female), with 76 (89%) patients completing all four treatments. In the modified intention-to-treat analysis, meaning all patients that received at least one FMT treatment (n = 82), primary endpoint was reached in 10 of 44 (23%) patients receiving donor FMT and in 2 of 38 (5%) patients receiving autologous FMT, (two-sided χ², p = 0.026). A further total of 26 patients received donor FMT in open-label extension of which 21 (81%) received all four treatments with 7/26 (27%) reaching the primary endpoint. Serious adverse events occurred in 6/44 (14%) in the donor FMT group vs 4/41 (10%) the autologous group. Two events were deemed related to the FMT treatment (pneumothorax after nasoduodenal placement and overnight hospitalization for abdominal pain one-day post FMT).

Conclusion

In this multi-centre randomized controlled trial, anaerobically processed, donor-selected, dual-route FMT demonstrated a higher likelihood of inducing clinical remission with donor FMT compared to autologous FMT at 8 weeks. The protocol proved feasible and generally safe. Larger trials are warranted to confirm efficacy and to optimize donor and patient selection strategies. ClinicalTrial.gov. Number: NCT05998213

References

1. Imdad A, Pandit NG, Zaman M, Minkoff NZ, Tanner-Smith EE, Gomez-Duarte OG, et al. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev. 2023;4(4):Cd012774.
2. Fuentes S, Rossen NG, van der Spek MJ, Hartman JH, Huuskonen L, Korpela K, et al. Microbial shifts and signatures of long-term remission in ulcerative colitis after faecal microbiota transplantation. Isme j. 2017;11(8):1877-89.
3. Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, et al. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015;149(1):110-8.e4.

Disclosure

The authors report no COI with regard to this study