Food as Medicine: How to Influence the Microbiome and Improve Symptoms in Patients with Irritable Bowel Syndrome.

PURPOSE OF REVIEW: This review highlights effects of dietary interventions on the gut microbiome and gastrointestinal symptoms in those with irritable bowel syndrome (IBS). RECENT FINDINGS: It is hypothesized that gut dysbiosis factors into the pathophysiology of IBS. Various diets that influence the microbiome and intestinal physiology may have therapeutic properties. At present, data suggests that implementation of personalized dietary interventions have a mixed, but overall positive effect on the gut microbiome and IBS symptoms. The effect of dietary modification on the gut microbiome and GI symptoms in patients with IBS is a topic that has garnered interest due to the increasing prevalence of IBS and heightened awareness of the importance of gut health. The composition of the gut microbiome may be modulated by promoting fiber intake and implementation of exclusionary diets and dietary supplements; however, additional studies are needed to provide evidence-based guidelines in this patient population.

Efficacy and Safety of Bezafibrate Alone or in Combination with Ursodeoxycholic Acid in Primary Biliary Cholangitis: Systematic Review and Meta-Analysis.

BACKGROUND: Bezafibrate (BZF) alone or in combination with ursodeoxycholic acid (UDCA) has been used to slow disease progression in patients with primary biliary cholangitis (PBC). We performed a systematic review and meta-analysis to assess the efficacy and harms of BZF monotherapy or combination therapy. METHODS: We performed a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception until January 2020, for randomized controlled clinical trials assessing BZF + UDCA versus UDCA monotherapy or BZF monotherapy versus UDCA monotherapy in PBC patients. Additionally, we systematically evaluated data on harms using seven observational studies. Pooled effect estimates were calculated for the outcomes of interest. The certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: We identified 7 randomized controlled trials with a total of 279 participants. Comparing BZF + UDCA to UDCA alone, a clinically significant improvement was observed in serum ALP with a mean difference (MD) of - 159.04 U/L (95% CI - 186.45 to - 131.62) and a reduction in gamma-glutamyltransferase (GGT) (MD - 106.94 IU/L; 95% CI - 151.99 to - 61.89), but not in total bilirubin (TB) or IgM levels. A statistically significant reduction in ALP levels was also noticed with BZF monotherapy compared to UDCA monotherapy. The effect of BZF + UDCA versus UDCA on mortality remains unclear. Across 5 observational studies including 106 patients, one death was reported due to advanced liver disease in an incomplete responder getting treatment with BZF + UDCA. Analysis of observational studies demonstrated improvement in pruritus intensity with BZF. CONCLUSIONS: Use of BZF alone or in combination with UDCA improved liver biochemistries in patients with PBC, but its effect on mortality, liver-related complications or quality of life remains unknown.

Impact of Obesity on Inflammatory Bowel Disease.

PURPOSE OF REVIEW: This review highlights recent work that evaluates the impact of obesity on inflammatory bowel disease (IBD) pathogenesis and management. RECENT FINDINGS: The impact of obesity on IBD prevalence, clinical course, and management, has been studied and described more so in recent years. Studies have shown that obesity increases IBD disease activity, leads to longer hospitalization courses, and increases the likelihood of the development of extraintestinal manifestations. Recent evidence has also suggested that obese IBD patients have a higher frequency of extended steroid treatment and increased use of antibiotics compared to non-obese IBD patients. The effect of obesity on patients with IBD is a topic that has garnered widespread interest in the last decade due to the increasing prevalence of both diseases. To date however, although there are still many unanswered questions. It is quite clear that obesity, and more specifically, visceral adiposity, affects numerous IBD-related outcomes in regard to pathogenesis, extra-intestinal manifestations, response to medical and surgical therapies, hospital length of stay, healthcare-related costs, and health-related quality of life. Future studies should include larger patient populations and evaluate additional factors that are altered in those with obesity including the gut microbiome, dietary patterns, and whether weight loss and/or degree of weight loss impact clinical outcomes.

Case of anti-Zic4 antibody-mediated cerebellar toxicity induced by dual checkpoint inhibition in head and neck squamous cell carcinoma.

Combined checkpoint inhibition therapy targeting the programmed cell death 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 pathways has been a successful approach in the treatment of metastatic melanoma, leading to its investigation in the treatment of head and neck squamous cell carcinoma (HNSCC) with PD-L1 expression. Despite the potential for excellent responses, an increased rate of autoimmune neurological toxicity and paraneoplastic conditions has been observed when using these treatment modalities. We present the case of a patient with metastatic HNSCC treated with combination ipilimumab/nivolumab who experienced severe cerebellar ataxia with a positive screen for the anti-Zic4 antibody. This is the first case, to our knowledge, of anti-Zic4 antibody-mediated cerebellar toxicity reported in association with HNSCC. Although the patient experienced an impressive partial response with dual checkpoint inhibition, he suffered grade 4 neurotoxicity. Despite exciting advances in cancer immunotherapy, clinicians must be aware of the rare, debilitating and possibly previously undescribed paraneoplastic and autoimmune toxicities that may occur.