Prebiotics and Probiotics for Gastrointestinal Disorders.

The complex role of the gut microbiome in the pathogenesis of gastrointestinal (GI) disorders is an emerging area of research, and there is considerable interest in understanding how diet can alter the composition and function of the microbiome. Prebiotics and probiotics have been shown to beneficially modulate the gut microbiome, which underlies their potential for benefit in GI conditions. Formulating specific recommendations for the public regarding these dietary supplements has been difficult due to the significant heterogeneity between strains, doses, and duration of treatment investigated across studies, as well as safety concerns with administering live organisms. This review aims to summarize the existing evidence for the use of prebiotics and probiotics in various GI disorders, paying special attention to strain-specific effects that emerged and any adverse effects noted.

Preventative and therapeutic potential of nutrition for inflammatory bowel diseases: A narrative review.

Diet strongly shapes the gut microbiome and metabolome, which in turn influence intestinal inflammation in patients with inflammatory bowel disease (IBD). Separate from inflammation and malnutrition, diet's direct interactions with the gastrointestinal system can also provoke or attenuate a host of nonspecific gastrointestinal symptoms. Given these multifaceted effects of diet on inflammation and symptoms, nutrition has been investigated for its potential roles in the prevention and treatment of IBD. This review presents epidemiological, observational cohort, and clinical trial evidence that underlie our current understanding of nutrition for prevention and treatment of IBD.

Herbal Medicines for the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used to identify potential articles for inclusion. Articles were screened and data were extracted by at least two investigators. Outcomes of interest included clinical response, clinical remission, endoscopic response, endoscopic remission, and safety. We identified 28 RCTs for 18 herbs. In pooled analyses, when compared with placebo, clinical response rates were significantly higher for Indigo naturalis (IN) (RR 3.70, 95% CI 1.97-6.95), but not for Curcuma longa (CL) (RR 1.60, 95% CI 0.99-2.58) or Andrographis paniculata (AP) (RR 0.95, 95% CI 0.71-1.26). There was a significantly higher rate of clinical remission for CL (RR 2.58, 95% CI 1.18-5.63), but not for AP (RR 1.31, 95% CI 0.86-2.01). Higher rates of endoscopic response (RR 1.56, 95% CI 1.08-2.26) and remission (RR 19.37, 95% CI 2.71-138.42) were significant for CL. CL has evidence supporting its use as an adjuvant therapy in active UC. Research with larger scale and well-designed RCTs, manufacturing regulations, and education are needed.

Prebiotics for Induction and Maintenance of Remission in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Prebiotics are nondigestible carbohydrates fermented by gut bacteria into metabolites that confer health benefits. However, evidence on their role for inflammatory bowel disease (IBD) is unclear. This study systematically evaluated the research on prebiotics for treatment of IBD. METHODS: A search was performed in PubMed, Embase, Cochrane, and Web of Science. Eligible articles included randomized controlled trials or prospective observational studies that compared a prebiotic with a placebo or lower-dose control in patients with IBD. Meta-analyses were performed using random-effects models for the outcomes of clinical remission, clinical relapse, and adverse events. RESULTS: Seventeen studies were included. For induction of clinical remission in ulcerative colitis (UC), the fructooligosaccharide (FOS) kestose was effective (relative risk, 2.75, 95% confidence interval, 1.05-7.20; n = 40), but oligofructose-enriched inulin (OF-IN) and lactulose were not. For maintenance of remission in UC, germinated barley foodstuff trended toward preventing clinical relapse (relative risk, 0.40; 95% confidence interval, 0.15-1.03; n = 59), but OF-IN, oat bran, and Plantago ovata did not. For Crohn's disease, OF-IN and lactulose were no different than controls for induction of remission, and FOS was no different than controls for maintenance of remission. Flatulence and bloating were more common with OF-IN; reported adverse events were otherwise similar to controls for other prebiotics. CONCLUSION: Prebiotics, particularly FOS and germinated barley foodstuff, show potential as effective and safe dietary supplements for induction and maintenance of remission in UC, respectively. The overall certainty of evidence was very low. There would be benefit in further investigation on the role of prebiotics as treatment adjuncts for IBD.

Prebiotics are nutrients fermented by gut microbes into healthful metabolites. This systematic review and meta-analysis examined the available research on the efficacy and safety of prebiotics for the treatment of inflammatory bowel diseases.

Recent trends and risk factors associated with Clostridioides difficile infections in hospitalized patients with inflammatory bowel disease.

BACKGROUND: Clostridioides difficile infections (CDIs) are common among patients with inflammatory bowel disease (IBD) and can mimic and exacerbate IBD flares, thus warranting appropriate testing during flares. AIMS: To examine recent trends in rates of CDI and associated risk factors in hospitalized IBD patients, which may better inform targeted interventions to mitigate the risk of infection. METHODS: This is a retrospective analysis using the Nationwide Readmissions Database from 2010 to 2020 of hospitalized individuals with Crohn's disease (CD) or ulcerative colitis (UC). Longitudinal changes in rates of CDI were evaluated using International Classification of Diseases codes. Multivariable logistic regression evaluated the association between patient- and hospital-related factors and CDI. RESULTS: There were 2,521,935 individuals with IBD who were hospitalized at least once during the study period. Rates of CDI in IBD-related hospitalizations increased from 2010 to 2015 (CD: 1.64%-3.32%, p < 0.001; UC: 4.15%-5.81%, p < 0.001), followed by a steady decline from 2016 to 2020 (CD: 3.15%-2.27%, p < 0.001; UC: 5.04%-4.27%, p < 0.001). In multivariable models, CDI was associated with the Charlson-Deyo comorbidity index, public insurance, and hospital size. CDI was associated with increased mortality. CONCLUSIONS: Rates of CDI among hospitalized patients with IBD had initially increased, but have declined since 2015. Increased comorbidity, large hospital size, public insurance, and urban teaching hospitals were associated with higher rates of CDI. CDI was associated with increased mortality in hospitalized patients with IBD. Continued vigilance, infection control, and treatment of CDI can help continue the trend of declining infection rates.

Increasing Rates of Bowel Resection Surgery for Stricturing Crohn's Disease in the Biologic Era.

BACKGROUND: The era of biologics is associated with declining rates of surgery for Crohn's disease (CD), but the impact on surgery for stricturing CD is unknown. Our study aimed to assess nationwide trends in bowel resection surgery for obstruction in CD since the introduction of infliximab for CD in 1998. METHODS: Using the Nationwide Inpatient Sample, we performed a nationwide analysis, identifying patients hospitalized for CD who underwent bowel resection for an indication of obstruction between 1998 and 2020 (era of biologics). Longitudinal trends in all CD-related resections and resection for obstruction were evaluated. Multivariable logistic regression identified patient and hospital characteristics associated with bowel resection surgery for obstruction. RESULTS: Hospitalizations for all CD-related resections decreased from 12.0% of all hospitalizations in 1998 to 6.9% in 2020, while hospitalizations for CD-related resection for obstructive indication increased from 1.3% to 2.0%. The proportion of resections for obstructive indication amongst all CD-related bowel resections increased from 10.8% in 1998 to 29.1% in 2020. In the multivariable models stratified by elective admission, the increasing year was associated with risk of resection for obstructive indication regardless of urgency (nonelective model: odds ratio, 1.01; 95% CI, 1.00-1.02; elective model: odds ratio, 1.06; 95% CI, 1.04-1.08). CONCLUSIONS: In the era of biologics, our findings demonstrate a decreasing annual rate of CD-related bowel resections but an increase in resection for obstructive indication. Our findings highlight the effect of medical therapy on surgical rates overall but suggest limited impact of current medical therapy on need of resection for stricturing disease.

In our nationwide analysis, rates of bowel resection for patients with Crohn's disease have declined since the approval of infliximab in 1998. However, rates of resection for obstruction in patients with Crohn's disease continue to increase.

Healthcare Utilization Among Patients Hospitalized With Gastrointestinal Diseases in the United States.

Background and Aims: Gastrointestinal (GI) disorders represent a significant burden on United States healthcare, but research assessing the relative contribution of individual GI disorders is lacking. We aimed to determine the relative impact of various GI conditions, as compared to non-GI conditions, on US hospital-related healthcare utilization. Methods: Hospitalization data from 2016 to 2018 were obtained from the Nationwide Readmissions Database. Outcomes included length of stay, hospital charges, 30-day readmissions, and death. Multivariable regression models evaluated each outcome, while adjusting for patient and hospital characteristics. Patients hospitalized for each GI indication were compared to individuals hospitalized for non-GI conditions. Results: 5,344,145 patients with GI and 68,901,595 patients with non-GI indications for hospitalization were included in our study. All GI indications were associated with increased odds for 30-day readmission compared to non-GI indications, with the highest being gastroparesis (adjusted odds ratio, 2.15; 95% confidence interval [CI], 2.09-2.22). Upper GI cancer had the highest relative increase in length of stay (2.31 days, 95% CI 2.20-2.42) and total charges ($23,441, 95% CI $21,296-25,587). Upper GI cancer, pancreatic cancer, and gallbladder/biliary cancer were associated with the highest odds of death. Conclusion: GI malignancies contributed significantly to utilization and death, possibly from advanced stage at hospitalization and systemic effects of malignancy. The high GI-specific readmission rates highlight the chronicity of GI conditions and the importance of optimizing digestive health to prevent recurrent admission.

ADS024, a single-strain live biotherapeutic product of Bacillus velezensis alleviates dextran sulfate-mediated colitis in mice, protects human colonic epithelial cells against apoptosis, and maintains epithelial barrier function.

Epithelial cell apoptosis and compromised gut barrier function are features of inflammatory bowel disease. ADS024 is a single-strain live biotherapeutic product (LBP) of Bacillus velezensis under development for treating ulcerative colitis (UC). The cytoprotective effects of the sterile filtrate of ADS024's secreted products on UC patient-derived colonic tissues, human primary colonic epithelial cells (HPEC), and human colonic epithelial T84 cells were evaluated. ADS024 filtrate significantly inhibited apoptosis and inflammation with reduced Bcl-2 Associated X-protein (BAX) and tumor necrosis factor (TNF) mRNA expression in fresh colonic explants from UC patients. Exposure to UC patient-derived serum exosomes (UCSE) induced apoptosis with increased cleaved caspase 3 protein expression in HPECs. ADS024 filtrate diminished the UCSE-mediated apoptosis by inhibiting cleaved caspase 3. TNFα and interferon-gamma (IFNγ) damaged epithelial barrier integrity with reduced transepithelial electrical resistance (TEER). ADS024 filtrate partially attenuated the TEER reduction and restored tight junction protein 1 (TJP1) expression. Oral live ADS024 treatment reduced weight loss, disease activity, colonic mucosal injury, and colonic expression of interleukin 6 (IL-6) and TNFα in dextran sodium sulfate (DSS)-treated mice with colitis. Thus, ADS024 may protect the colonic epithelial barrier in UC via anti-inflammatory, anti-apoptotic, and tight-junction protection mechanisms.

Biologic Treatment Withdrawal: Two Sides of a Coin.

Biologic Treatment Withdrawal: Two Sides of a CoinThe advent of monoclonal antibody (biologic) therapies ushered in a wave of highly effective yet relatively safe treatments for inflammatory bowel diseases; their use predicated on assertively controlling intestinal inflammation to reduce disease-related complications has accelerated their adoption in clinical practice.1-3 However, despite the overall advantages of biologic therapies, patients often express hesitation initiating them. The concern is for fear of adverse effects (particularly, infections and malignancy), inconvenience, cost, and the psychologic barrier of having to receive an intravenous or injectable drug "for the rest of my life."