The Brain-Gut-Microbiome Axis.

Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression. A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases

Anaerobic biosynthesis of the lower ligand of vitamin B12

Vitamin B(12) (cobalamin) is required by humans and other organisms for diverse metabolic processes, although only a subset of prokaryotes is capable of synthesizing B(12) and other cobamide cofactors. The complete aerobic and anaerobic pathways for the de novo biosynthesis of B(12) are known, with the exception of the steps leading to the anaerobic biosynthesis of the lower ligand, 5,6-dimethylbenzimidazole (DMB). Here, we report the identification and characterization of the complete pathway for anaerobic DMB biosynthesis. This pathway, identified in the obligate anaerobic bacterium Eubacterium limosum, is composed of five previously uncharacterized genes, bzaABCDE, that together direct DMB production when expressed in anaerobically cultured Escherichia coli. Expression of different combinations of the bza genes revealed that 5-hydroxybenzimidazole, 5-methoxybenzimidazole, and 5-methoxy-6-methylbenzimidazole, all of which are lower ligands of cobamides produced by other organisms, are intermediates in the pathway. The bza gene content of several bacterial and archaeal genomes is consistent with experimentally determined structures of the benzimidazoles produced by these organisms, indicating that these genes can be used to predict cobamide structure. The identification of the bza genes thus represents the last remaining unknown component of the biosynthetic pathway for not only B(12) itself, but also for three other cobamide lower ligands whose biosynthesis was previously unknown. Given the importance of cobamides in environmental, industrial, and human-associated microbial metabolism, the ability to predict cobamide structure may lead to an improved ability to understand and manipulate microbial metabolism

Impact of the COVID-19 Pandemic on Patient Preferences and Decision Making for Symptomatic Urolithiasis

Background: Pandemic restrictions have changed how patients approach symptomatic kidney stones. We used a mixed-methods digital ethnographic approach to evaluate social media discussions about patient concerns and preferences for urolithiasis care during the COVID-19 pandemic. Materials and Methods: We retrospectively analyzed kidney stone-related discussions on a large social media platform using qualitative analysis and natural language processing-based sentiment analysis. Posts were mined for demographic details, treatments pursued, and health care encounters. Pre-COVID-19 (January 1, 2020-February 29, 2020) and COVID-19 (March 1, 2020-June 1, 2020) posts were extracted from the popular online Reddit discussion board, r/KidneyStones, which is dedicated to discussions related to urolithiasis. Results: We extracted n = 649 posts (250 pre-COVID-19, 399 COVID-19); 150 from each cohort underwent thematic analysis and data extraction. Quantitative sentiment analysis was performed on 418 posts (179 pre-COVID-19, 239 COVID-19) that described stone-related decision making before intervention. Notable discussion themes during COVID-19 focused on barriers to care and concerns about stone management. Discussants exhibited more negative and anxious tones during COVID-19, based on sentiment analysis (p \u3c 0.01). Patient preferences shifted away from in-person visits and procedures (p \u3c 0.001). Mean reported stone size among those visiting emergency room (ER) increased from 5.1 to 10.5 mm (p \u3c 0.001). The proportion of discussants preferring conservative management with stones ≥10 mm increased (12.5% pre-COVID-19 vs 26% during COVID-19, p = 0.002). Opioid mentions increased from 9% to 27% of posts (p \u3c 0.001) and were most associated with conservative management discussions. Conclusions: Online discussion forums provide contemporaneous insight into patients\u27 experiences during a time when traditional patient-centered research methodologies are limited due to social distancing. During the pandemic, patients with symptomatic kidney stones expressed anxiety regarding outpatient encounters and reluctance toward procedural intervention. Patients opted instead for at-home conservative treatment beyond clinical guidelines and reserved ER visits for larger stones, potentially causing self-harm. Opioid discussions proliferated, an alarming consequence of the pandemic

The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications

Background & aimsBased largely on results from preclinical studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome, and the nervous system. Limited data obtained in human beings suggest that alterations in these interactions may play a role in several brain gut disorders.MethodsWe reviewed the preclinical and clinical literature related to the topic of brain gut microbiome interactions.ResultsWell-characterized bidirectional communication channels, involving neural, endocrine, and inflammatory mechanisms, exist between the gut and the brain. Communication through these channels may be modulated by variations in the permeability of the intestinal wall and the blood-brain barrier. Brain gut microbiome interactions are programmed during the first 3 years of life, including the prenatal period, but can be modulated by diet, medications, and stress throughout life. Based on correlational studies, alterations in these interactions have been implicated in the regulation of food intake, obesity, and in irritable bowel syndrome, even though causality remains to be established.ConclusionsTargets within the brain gut microbiome axis have the potential to become targets for novel drug development for brain gut disorders

The Brain-Gut-Microbiome Axis.

Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression. A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases