Symptom profile of patients with intestinal methanogen overgrowth: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Archaea constitute one of the main three domains of the tree of life, distinct from eukaryotes and bacteria. Excessive luminal loads of methanogenic archaea (intestinal methanogen overgrowth, IMO) have been implicated in the pathophysiology of various diseases, including constipation. To elucidate the phenotypical presentation of IMO, we performed a systematic review and meta-analysis of the prevalence and severity of gastrointestinal (GI) symptoms in subjects with IMO as compared to subjects without IMO. METHODS: Electronic databases, including OVID MEDLINE and Cochrane Database from inception until September 2023, were systematically searched. Prevalence rates, odds ratios (ORs), standardized mean difference (SMD) and 95% confidence intervals (CIs) of symptoms were calculated. RESULTS: Nineteen studies were included (1293 patients with IMO and 3208 controls). IMO patients exhibited various GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%). Patients with IMO had a significantly higher prevalence of constipation as compared to controls (47% vs. 38%, OR 2.04, 95% CI 1.48-2.83, p<0.0001) along with lower prevalence of diarrhea (37% vs. 52%, OR 0.58, 95% CI 0.37-0.90, p=0.01) and nausea (32% vs. 45%, OR 0.75, 95% CI 0.60-0.94, p=0.01). Patients with IMO had higher severity of constipation (SMD 0.77; 95% CI 0.11-1.43, p=0.02) and lower severity of diarrhea (SMD -0.71, 95% CI -1.39, -0.03, p=0.04). Significant heterogeneity was detected. CONCLUSION: Patients with IMO exhibit a higher rate and severity of constipation along with lower rate and severity of diarrhea. The distinct phenotype of IMO patients should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies.

Elemental Diet as a Therapeutic Modality: A Comprehensive Review.

Elemental diets have been employed for the management of various diseases for over 50 years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn's disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.

Antifungal effects of echinocandins diminish when exposed to intestinal lumen contents: a finding with potentially significant clinical implications.

Echinocandins, a prominent class of antifungals, are known for their broad-spectrum activity and favorable safety profiles. However, their bioavailability and efficacy via oral route are suboptimal. In this study, caspofungin and micafungin, the two most commonly used echinocandins, were evaluated in various in vitro environments simulating intestinal lumen. The results revealed that while both antifungals are effective in standard medium, their efficacy significantly diminishes in the presence of human small bowel aspirates and bovine bile. The study suggests that bowel contents and specifically bile acids may be a suppressive component, hindering the antifungal effects of echinocandins. This novel exploration sheds light on the poor oral bioavailability of echinocandins. The findings imply that echinocandins alone, regardless of administration route, may not be optimal for gastrointestinal (GI) fungal infections or invasive fungal infections originating from intestinal translocation. Further clinical investigations are warranted to validate and expand upon these observations.

Allergies and risk of head and neck cancer: a case-control study.

Although the relationship between allergies and cancer has been investigated extensively, the role of allergies in head and neck cancer (HNC) appears less consistent. It is unclear whether allergies can independently influence the risk of HNC in the presence of substantial environmental risk factors, including consumption of alcohol, betel quid, and cigarettes. This study aims to find this association. We examined the relationship between allergies and HNC risk in a hospital-based case-control study with 300 cases and 375 matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals, controlling for age, sex, tobacco smoking and opium usage history, alcohol consumption, and socioeconomic status. Our study showed a significant reduction in the risk of HNC associated with allergy symptoms after adjusting for confounders. The risk of HNC was greatly reduced among those with any type of allergy (OR 0.42, 95% CI 0.28, 0.65). The ORs were considerably reduced by 58-88% for different kinds of allergies. The risk of HNC reduction was higher in allergic women than in allergic men (71% vs. 49%). Allergies play an influential role in the risk of HNC development. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are necessary to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help to devise effective strategies to reduce and treat HNC.

Extracellular and intracellular antiviral effects of ultraviolet A against severe acute respiratory syndrome coronavirus-2 are variant-independent.

Under controlled settings, narrow-band ultraviolet A (UVA) exposure exerts antiviral effects both in vivo and in vitro. The effect is thought to be mediated via direct effect on viral particles and indirectly, by modulation of metabolic pathways of host cells. We aimed to explore the extracellular and intracellular antiviral effects of UVA exposure against Alpha, Beta, and Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Vero E6 kidney normal epithelial cells and human tracheal epithelial cells were infected with Alpha, Beta, and Delta variants in a BSL-3 laboratory. To assess extracellular effects, SARS-CoV-2 variants were directly exposed to a single dose of UVA prior to infection of the host cells (Vero E6 kidney normal epithelial cells and human tracheal epithelial cells) The intracellular effects of UVA were assessed by first infecting the cells with SARS-CoV-2 variants followed by UVA treatment of infected cell monolayers. Efficacy was quantified by both plaque reduction assay and quantitative real-time polymerase chain reaction. Additionally, transcriptomic analysis was performed on exposed Vero E6 cells to assess differentially expressed genes and canonical pathways as compared to controls. RESULTS: SARS-CoV-2 Alpha, Beta and Delta variants are susceptible to UVA exposure prior to infection of Vero E6 cells. Importantly, the UVA-driven reduction in Delta variant load could be reproduced in human primary tracheal cells. Beta and Delta variants load also significantly decreased during Vero E6 cells intracellular experiments. UVA-driven reductions in viral loads ameliorate several host metabolic pathways, including canonical pathways related to viral infection and interferon signaling. CONCLUSION: Narrow-band UVA exhibits both extracellular effects on SARS-CoV-2 viral particles and intracellular effects on infected cells with SARS-CoV-2. Efficacy appears to be variant independent.