Microbiome 2.0: lessons from the 2024 Gut Microbiota for Health World Summit.

This Meeting Summary highlights the key insights from the 12th meeting of the Gut Microbiota for Health World Summit, held in Washington, DC, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM). Through a 2-day series of plenary sessions, workshops, a poster session, and live discussions involving thought leaders, physicians, researchers, and representatives from the Food and Drug Administration and the pharmaceutical industry, the conference attendees focused on the strategies and challenges in developing microbiome-based therapies to prevent and treat human disease. The conference highlighted progress in the field, including the recently successful introduction of 2 new fecal microbial transplantation-based products into the clinical setting, and the continuing development of next-generation probiotics. However, to continue to advance microbiome-directed treatments, three key themes emerged during the meeting, including (1) better methods to identify actionable targets in the microbiome (2) developing effective strategies to manipulate the microbiome (3) aligning microbiome-based therapies with existing treatment paradigms in the real world.

Specific bacterial co-abundance groups are associated with inflammatory status in patients with ulcerative colitis.

BACKGROUND AND AIMS: While there is increasing interest in microbiome-directed therapies for patients with ulcerative colitis (UC), the identification of microbial targets remains elusive, underlining the need for novel approaches. METHODS: Utilizing metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease, available via the IBD Plexus Program of the Crohn's & Colitis Foundation, we used a tree-based dichotomous approach to assemble distinct clusters of species-level bacterial co-abundance groups (CAGs). We evaluated the abundance of bacterial CAGs and fungal taxa during remission (n=166) and activity (n=46). We examined if the bacterial CAGs identified in our cohorts were conserved in 2 healthy cohorts and in a Korean UC cohort. RESULTS: CAG3 and CAG8, dominated by bacteria from family Lachnospiraceae, were associated with remission. Low CAG8 and elevated Candida genus were predictive of active UC. Constituents from CAG8 were influential hub species of the remission-associated microbial UC network, including Ruminococcus gnavus, Erysipelatoclostridium ramosum, Blautia and Dorea species. These hub species interactions were preserved in 2 healthy cohorts and were partially recapitulated in a Korean UC cohort. CAG8 abundance correlated with the secondary bile acid production pathway. Bacterial CAGs did not correlate with Candida, however Bifidobacterium adolescentis and Alistipes putredinis were negatively associated with Candida. CONCLUSIONS: Lachnospiriceae-dominated bacterial CAGs were associated with remission in UC, with key bacterial interactions within the CAG also observed in 2 healthy cohorts and a Korean UC cohort. Bacterial CAG-based analyses may help to inform the design of candidate consortia for microbiome-based therapeutics.

Microbial butyrate capacity is reduced in inflamed mucosa in patients with ulcerative colitis.

Reduced butyrate-production capacity has been reported in fecal microbial communities in patients with active ulcerative colitis. However, the butyrate-production capacity of the mucosal microbiome from active vs quiescent mucosa in ulcerative colitis has been unexplored. We sought to determine the diversity and relative abundance of mucosal bacterial and fungal communities from endoscopically active vs quiescent mucosa in patients with UC, and aimed to predict contributions of mucosal microbial communities to butyrate synthesis. Systematic, segmental right- and left-sided biopsies were obtained from endoscopically active (n = 13) or quiescent (n = 17) colonic mucosa, among 15 patients with pan-colonic ulcerative colitis. Dietary fiber intake of patients was performed using the validated five-item FiberScreen questionnaire. Amplicon sequencing of mucosal bacteria and fungi was performed. The diversity and relative abundance of mucosal bacterial and fungal taxa were quantified, and predicted contributions to butyrate synthesis were ascertained. Bacterial alpha and beta diversity were similar between active vs quiescent mucosa. Butyrogenic taxa were significantly increased in quiescence, including Butyricimonas, Subdoligranulum, and Alistipes. Predicted butyrate kinase activity was significantly and concomitantly increased in quiescent mucosa. Fiber intake was positively correlated with butyrogenic microbes. Compared to mucosal bacterial prevalence, mucosal fungi were detected in low prevalence. Butyrogenic microbes are relatively increased in quiescent mucosa in ulcerative colitis, and may be related to increased fiber intake during quiescence. Manipulation of the mucosal microbiome towards butyrate-producing bacteria may be associated with endoscopic quiescence.

Colorectal Neoplasia in Asian Americans Undergoing First Time Asymptomatic Average-risk Screening Colonoscopies.

GOALS: We identified the prevalence and subtype of colorectal neoplasia removed during index screening colonoscopies in a large Asian American population. BACKGROUND: Asian Americans are the fastest growing demographic group in the United States yet there is a paucity of data on the characteristics of colorectal neoplasia found in this cohort. STUDY: Cross-sectional study of 2208 index colonoscopies performed on average-risk Asian and White patients at a large, tertiary academic center. Patients were identified via diagnostic or procedure codes between 2015 and 2020, with retrospective classification of polyp histopathology. Univariate and multivariate analysis were performed to identify risk factors associated with colorectal neoplasia. RESULTS: A total of 2208 patients were identified, of which 1085 were Asian. When adjusted for age and sex, Asians were as likely as Whites to have any type of colorectal neoplasia [44.2% vs. 43.5%, odds ratio (OR)=0.93, (CI: 0.78-1.11)]. On multivariate analysis, Asians were less likely to have sessile serrated polyps (5.5% vs. 9.9%, OR=0.53, 95% CI: 0.38-0.73) and more likely to have tubular adenomas in the left colon (22.6% vs. 18.0%, OR=1.33, 95% CI: 1.08-1.64) compared with Whites. CONCLUSIONS: Quality measures, such as sessile serrated polyp detection rates, may need to take into account demographic factors such as race. The prevalence of colorectal neoplasia among Asian Americans is substantial and warrants efforts to promote optimal uptake of colorectal cancer screening tests.

Efficacy and Safety of Hyperbaric Oxygen Therapy in Fistulizing Crohn's Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen in a pressurized chamber, increasing tissue oxygen levels and regulating inflammatory pathways. Mounting evidence suggests that HBOT may be effective for inflammatory bowel disease. Our systematic review and meta-analysis aimed to quantify the efficacy and safety of HBOT in fistulizing Crohn's disease (CD). METHODS: A systematic review was conducted using the EMBASE, Web of Science, Pubmed, and Cochrane Library databases according to the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" criteria. Study bias was assessed using the Cochrane Handbook guidelines. RESULTS: Sixteen studies with 164 patients were included in the analysis. For all fistula subtypes, the pooled overall clinical response was 87% (95% CI: 0.70-0.95, I2 = 0) and the pooled clinical remission was 59% (95% CI: 0.35-0.80, I2 = 0). The overall clinical response was 89%, 84%, and 29% for perianal, enterocutaneous, and rectovaginal fistulas, respectively. On meta-regression, hours in the chamber and the number of HBOT sessions were not found to correlate with clinical response. The pooled number of adverse events was low at 51.7 per 10,000 HBOT sessions for all fistula types (95% CI: 16.8-159.3, I2 = 0). The risk of bias was observed across all studies. CONCLUSION: HBOT is a safe and potentially effective treatment option for fistulizing CD. Randomized control trials are needed to substantiate the benefit of HBOT in fistulizing CD.

Dynamics of the Gut Mycobiome in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC). However, it remains unclear if fungal composition is altered during active versus quiescent disease. METHODS: We analyzed clinical and metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's & Colitis Foundation. We evaluated the fungal composition of fecal samples from 421 patients with UC during clinical activity and remission. Within a longitudinal subcohort (n = 52), we assessed for dynamic taxonomic changes across alterations in clinical activity over time. We examined if fungal amplicon sequence variants and fungal-bacterial relationships were altered during activity versus remission. Finally, we classified activity in UC using a supervised machine learning random forest model trained on fungal abundance data. RESULTS: During clinical activity, the relative abundance of genus Candida was increased 3.5-fold (P-adj < 1 × 10-4) compared with during remission. Patients with longitudinal reductions in clinical activity demonstrated parallel reductions in Candida relative abundance (P < .05). Candida relative abundance correlated with Parabacteroides diastonis, Faecalibacterium prausnitzii, and Bacteroides dorei relative abundance (P < .05) during remission; however, these correlations were disrupted during activity. Fungal abundance data successfully classified patients with active or quiescent UC (area under the curve ∼0.80), with Candida relative abundance critical to the success of the model. CONCLUSIONS: Clinical activity in UC is associated with an increased relative abundance of Candida, cross-sectionally and dynamically over time. The role of fecal Candida as a target for therapeutics in UC should be evaluated.

Predictors and Etiologies of Clinical Relapse Among Patients With Ulcerative Colitis in Deep Remission.

GOAL: The objective of this study was to evaluate for potential predictors and etiologies of clinical relapse among patients with ulcerative colitis in deep remission. BACKGROUND: Patients displaying deep (endoscopic and histologic) remission have a decreased cumulative risk of relapse in ulcerative colitis of <10% per year, but predictors and etiologies of relapse in this population are poorly understood. MATERIALS AND METHODS: We performed a retrospective cohort study utilizing electronic medical records at Tufts Medical Center to identify patients in deep remission, classified as having both endoscopic remission (Mayo Endoscopic Score of 0 or 1) and histologic remission (Simplified Geboes Score 0.2). We evaluated the cumulative risk of clinical relapse following attainment of deep remission and examined predictors and etiologies of relapse. RESULTS: Among 139 patients with ulcerative colitis in deep remission, the cumulative risk of relapse was <10% and <20% at 1 and 2 years. Patients with complete normalization of mucosa (Geboes=0) and normalization of C-reactive protein (<7.48 mg/dL) at the time of remission were associated with a lower risk of relapse. Discontinuation of therapy was the most commonly identified etiology of relapse. CONCLUSIONS: Patients in deep remission have a 1-year risk of clinical relapse of <10%, with those demonstrating a non-normalized mucosa or elevated C-reactive protein predictive of persistent relapse risk. Discontinuation of therapy or minor histologic changes may drive relapse among those in deep remission.

Rising Inpatient Utilization and Costs of Cannabis Hyperemesis Syndrome Hospitalizations in Massachusetts After Cannabis Legalization.

GOALS: We described the demographics, inpatient utilization, and cost of services among patients hospitalized for putative cannabinoid hyperemesis syndrome (CHS) predating and postdating cannabis legalization in Massachusetts. BACKGROUND: As the recreational use of cannabis has been widely legalized nationally, the resulting shifts in clinical presentation, health care utilization, and estimated costs of CHS hospitalizations remain unclear in the postlegalization era. STUDY: We performed a retrospective cohort study among patients admitted to a large urban hospital between 2012 and 2021, before and after the date of cannabis legalization in Massachusetts (Dec 15, 2016). We examined the demographic and clinical characteristics of patients admitted for putative CHS, the utilization of hospital services, and estimated inpatient costs pre and postlegalization. RESULTS: We identified a significant increase in putative CHS hospitalizations pre and post-cannabis legalization in Massachusetts (0.1% vs 0.02% of total admissions per time period, P < 0.05). Across 72 CHS hospitalizations, patient demographics were similar pre and postlegalization. Hospital resource utilization increased postlegalization, with increased length of stay (3 d vs 1 d, P < 0.005), and need for antiemetics ( P < 0.05). Multivariate linear regression confirmed that postlegalization admissions were independently associated with increased length of stay ( Β = 5.35, P < 0.05). The mean cost of hospitalization was significantly higher postlegalization ($18,714 vs $7460, P < 0.0005), even after adjusting for medical inflation ($18,714 vs $8520, P < 0.001) with intravenous fluid administration and endoscopy costs increased ( P < 0.05). On multivariate linear regression, hospitalization for putative CHS during postlegalization predicted increased costs ( Β = 10,131.25, P < 0.05). CONCLUSIONS: In the postlegalization era of cannabis in Massachusetts, we found increased putative CHS hospitalizations, with a concomitant increased length of hospital stay and total cost per hospitalization. As cannabis use increases, the recognition and costs of its deleterious effects are necessary to incorporate into future clinical practice strategies and health policy.