Coenzyme A metabolism: a key driver of gut microbiota dynamics and metabolic profiles

The role of the gut microbiome in chronic liver disease: the clinical evidence revised.

East Meets West: The Increasing Incidence of Inflammatory Bowel Disease in Asia as a Paradigm for Environmental Effects on the Pathogenesis of Immune-Mediated Disease

Understanding the role of gut microbiome–host metabolic signal disruption in health and disease

Genetics and Environmental Interactions Shape the Intestinal Microbiome to Promote Inflammatory Bowel Disease Versus Mucosal Homeostasis

Transfer of Intestinal Microbiota From Lean Donors Increases Insulin Sensitivity in Individuals With Metabolic Syndrome

Gut microbe composition and metabolic syndrome

The Intestinal Metabolome: An Intersection Between Microbiota and Host

The Gut Microbiome in Health and Disease

Nonalcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease and second indication for liver transplantation in the Western world. Effective therapy is still not available. Previously we showed a critical role for caspase-2 in the pathogenesis of nonalcoholic steatohepatitis (NASH), the potentially progressive form of NAFLD. An imbalance between free coenzyme A (CoA) and acyl-CoA ratio is known to induce caspase-2 activation. We aimed to evaluate CoA metabolism and the effects of supplementation with CoA precursors, pantothenate and cysteine, in mouse models of NASH. CoA metabolism was evaluated in methionine-choline deficient (MCD) and Western diet mouse models of NASH. MCD diet-fed mice were treated with pantothenate and N-acetylcysteine or placebo to determine effects on NASH. Liver free CoA content was reduced, pantothenate kinase (PANK), the rate-limiting enzyme in the CoA biosynthesis pathway, was down-regulated, and CoA degrading enzymes were increased in mice with NASH. Decreased hepatic free CoA content was associated with increased caspase-2 activity and correlated with worse liver cell apoptosis, inflammation, and fibrosis. Treatment with pantothenate and N-acetylcysteine did not inhibit caspase-2 activation, improve NASH, normalize PANK expression, or restore free CoA levels in MCD diet-fed mice. In mice with NASH, hepatic CoA metabolism is impaired, leading to decreased free CoA content, activation of caspase-2, and increased liver cell apoptosis. Dietary supplementation with CoA precursors did not restore CoA levels or improve NASH, suggesting that alternative approaches are necessary to normalize free CoA during NASH.

Gut Microbiota and Its Possible Relationship With Obesity

SummaryHost-microbiota interactions create a unique metabolic milieu that modulates intestinal environments. Integration of 16S ribosomal RNA (rRNA) sequences and mass spectrometry (MS)-based lipidomics has a great potential to reveal the relationship between bacterial composition and the complex metabolic network in the gut. In this study, we conducted untargeted lipidomics followed by a feature-based molecular MS/MS spectral networking to characterize gut bacteria-dependent lipid subclasses in mice. An estimated 24.8% of lipid molecules in feces were microbiota-dependent, as judged by > 10-fold decrease in antibiotic-treated mice. Among these, there was a series of unique and microbiota-related lipid structures, including acyl alpha-hydroxyl fatty acid (AAHFA) that was newly identified in this study. Based on the integrated analysis of 985 lipid profiles and 16S rRNA sequence data providing 2,494 operational taxonomic units, we could successfully predict the bacterial species responsible for the biosynthesis of these unique lipids, including AAHFA.

Gut microbiota, a special group of microbiotas in the human body, contributes to health in a way that can't be ignored. In recent years, Mendelian randomization, which is a widely used and successful method of analyzing causality, has been investigated for the relationship between the gut microbiota and related diseases. Unfortunately, there seems to be a shortage of systematic bibliometric analysis in this field. Therefore, this study aims to investigate the research progress of Mendelian randomization for gut microbiota through comprehensive bibliometric analysis. In this study, publications about Mendelian randomization for gut microbiota were gathered from 2013 to 2023, utilizing the Web of Science Core Collection as our literature source database. The search strategies were as follows: TS = (intestinal flora OR gut flora OR intestinal microflora OR gut microflora OR intestinal microbiota OR gut microbiota OR bowel microbiota OR bowel flora OR gut bacteria OR intestinal tract bacteria OR bowel bacteria OR gut metabolites OR gut microbiota) and TS = (Mendelian randomization). VOSviewer (version 1.6.18), CiteSpace (version 6.1.R1), Microsoft Excel 2021, and Scimago Graphica were employed for bibliometric and visualization analysis. According to research, from January 2013 to August 2023, 154 publications on Mendelian randomization for gut microbiota were written by 1053 authors hailing from 332 institutions across 31 countries and published in 86 journals. China had the highest number of publications, with 109. Frontiers in Microbiology is the most prolific journal, and Lei Zhang has published the highest number of significant articles. The most popular keywords were "Mendelian randomization," "gut microbiota," "instruments," "association," "causality," "gut microbiome," "risk," "bias," "genome-wide association," and "causal relationship." Moreover, the current research hotspots in this field focus on utilizing a 2-sample Mendelian randomization to investigate the relationship between gut microbiota and associated disorders. This research systematically reveals a comprehensive overview of the literature that has been published over the last 10 years about Mendelian randomization for gut microbiota. Moreover, the knowledge of key information in the field from a bibliometric perspective may greatly facilitate future research in the field.

Chronic intermittent hypoxia (CIH) is the prominent signature of highly prevalent obstructive sleep apnea (OSA) pathophysiology, which leads to increased risk and aggravation of atherosclerotic cardiovascular diseases. However, whether intestinal microbiota is implicated in the mechanisms linking CIH to arteriosclerosis (AS) pathogenesis remains unclear. The association of CIH with the development of altered gut microbiota (GM) may provide the opportunity to develop preventive strategies for atherosclerotic cardiovascular risk reduction. Animal models of apolipoprotein E-deficient (apoE-/-) mice treated with high-fat diet (HFD) and subjected to CIH conditions was applied to mimic the AS observed in patients with OSA. The physiological status and atherosclerotic lesion formation were confirmed by histological analysis. 16S rDNA sequencing of fecal samples was conducted to determine the changes in gut microbial composition. Morphometric analysis demonstrated that CIH caused aggravated atherosclerotic lesions and facilitated AS in apoE-/- mice treated with HFD. The gut bacteria was significantly varied in AS and AS+CIH mice compared with that in the control mice. Significantly perturbed GM profiles were detected in AS mice with and without CIH, with altered microbial α- and β- diversity and shifts in bacterial compositions at phylum and genus levels. While the difference between AS and AS+CIH was observed at different bacteria taxa levels. Aggravation of reduced Sutterella and increased Halomonas, Halomonadaceae and Oceanospirillales was noted in CIH-treated AS mice. The correlation of intestinal bacterial parameters with pathological changes in artery indicated complicated interactions under CIH-induced GM dysbiosis. Furthermore, the gut microbial functions in the potential ability of replication recombination and repair proteins, glycan biosynthesis and metabolism, as well as metabolism of cofactors and vitamins were identified to be further suppressed by CIH. Our findings demonstrated a causal effect of CIH on GM alterations in AS mice and suggested that the disordered GM features in AS development were deteriorated by CIH, which may be associated with AS aggravation. Preventative strategies targeting gut microbiome are highly recommended for intervention of OSA-related AS.

The role of a tetR transcriptional regulatory gene (SAV7471) in avermectin production in the Gram-positive soil bacterium Streptomyces avermitilis was investigated by gene deletion, complementation, and overexpression experiments. Gene deletion of the SAV7471 open reading frame resulted in avermectin overproduction. The deletion also resulted in overexpression of SAV7472-SAV7473 transcripts, which encode a protein of unknown function and a flavoprotein possibly involved in pantothenate and coenzyme A (CoA) metabolism. EMSAs and footprinting assays showed that SAV7471 can bind to two palindromic sequences with high similarity in the intergenic region between SAV7471 and SAV7472, a region that contains the apparent transcription start sites for each gene detected by rapid amplification of 5' cDNA ends (5'-RACE). In addition to SAV7472-SAV7473, at least two genes (SAV1104 and SAV1258) involved in CoA metabolism are negatively controlled by SAV7471. By negatively regulating the transcription of the target genes SAV7472-SAV7473 and other genes involved in CoA metabolism, SAV7471 may affect cellular metabolic flux and may thereby indirectly regulate avermectin biosynthesis.

Sex hormones play a crucial role in shaping gut microbiome composition and metabolism, with significant implications for mental health. This study investigated the effects of sex hormones and the psychotropic drug aripiprazole on the gut microbiome, using a novel in vitro colonic fermentation model adapted from the PolyFermS system. Fecal samples from four male and female donors were used to develop sexually divergent models, with the female model subjected to hormonal treatments mimicking different phases of the menstrual cycle. Microbiome composition and short-chain fatty acid (SCFA) metabolism were analyzed. The results demonstrated that sex hormones significantly influenced microbiota structure and diversity, with the female model exhibiting reduced α-diversity and distinct bacterial associations with SCFAs. Hormonal fluctuations across menstrual phases induced specific shifts in bacterial composition, notably increasing Bacteroidota while decreasing Bacillota and Pseudomonadota. In the female model, aripiprazole treatment led to increased microbial diversity and altered SCFA profiles, although the changes in SCFAs were not statistically significant (P > 0.05). Differential abundance analysis revealed sex-specific enrichment of bacterial genera, such as Eubacterium coprostanoligenes and Agathobacter. These findings underscore the importance of considering sex-specific microbiome profiles and hormonal influences when optimizing psychotropic treatments for mental health disorders.IMPORTANCEThe gut microbiome plays a crucial role in human health, affecting metabolism, immunity, and brain function. However, the role of sex hormones in shaping the gut microbiome composition and metabolism remains largely unexplored. This study introduces a novel in vitro colonic fermentation model to investigate the effects of sex hormone fluctuations and psychotropic drug exposure on the gut microbiome. By simulating a sexually divergent human colon environment and mimicking hormonal variations throughout the menstrual cycle, this model provides a controlled setting for studying microbiome response to external stimuli. Our findings revealed that sex hormones, such as estrogen, progesterone, and testosterone, shape microbial diversity and alter the microbiome composition compared to the control group. Additionally, this study examined the effect of psychotropic drug exposure on the microbiota of a simulated female colon, revealing alterations in the microbial composition and metabolism. These results highlight the importance of considering the role of the gut microbiome in drug response, given the widespread use of psychiatric medications, particularly among women. This novel colonic fermentation model offers a valuable tool for studying sex-specific microbiome dynamics and their broader implications for health.