Intestinal dysbiosis is a hallmark of alcohol-associated liver disease (ALD) characterized by a higher abundance of unfavorable species and a reduction of beneficial species. In this study, we aimed to analyze the bacterial proteome of stool samples from patients with alcohol-associated hepatitis (AH) (n = 80), alcohol use disorder (AUD; n = 20), and controls (n = 19) from an international multicenter cohort using quantitative tandem mass tag (TMT)-based metaproteomic profiling. We validated our results in an independent multicenter cohort of 72 patients with AH at the genomic level using qPCR. We detected 2,364 bacterial proteins and identified distinct metaproteomic signatures separating controls, patients with AUD, and AH. Patients with AUD and AH were characterized by depletion of Firmicutes-derived proteins and enrichment of proteins from Bacteroidetes, Proteobacteria, and Actinobacteria. Eighteen bacterial proteins increased with disease severity, many with multifunctional “moonlighting” roles, including enolase and hexokinase. DUF6383 domain-containing protein from Parabacteroides distasonis is correlated with histological injury, inflammatory cell infiltration, and is linked to neutrophil degranulation in the host. Patients with a high abundance of DUF6383 domain-containing protein had significantly lower 90-day survival, and this association was validated by qPCR at the genomic level in a second cohort. Our findings show that microbial proteins are associated with disease severity and progression, and that DUF6383 domain-containing protein from P. distasonis is a potential prognostic biomarker for AH.
Binge Eating Disorder (BED), the most prevalent eating disorder worldwide, is characterized by recurrent episodes of uncontrolled food intake accompanied by marked psychological distress in the absence of regular compensatory behaviors. While behavioral and neurobiological frameworks have traditionally dominated research, converging evidence now positions the gut microbiota as a critical mediator of BED pathophysiology through bidirectional microbiota-gut-brain axis (MGBA) communication. This review synthesizes current knowledge of gut microbial remodeling in BED, elucidating how compositional alterations contribute to pathogenesis through disrupted satiety signaling, altered neurotransmitter metabolism, immune-inflammatory cascades, and vagal dysfunction. Recent evidence highlights BED-specific depletion of fermentative taxa, including Pediococcus, Catenibacterium, and Megasphaera, with depletion of Pediococcus correlated with reduced cardiac vagal tone. The mechanistic landscape encompasses short-chain fatty acid (SCFA)-mediated appetite modulation, α-MSH mimicry by bacterial caseinolytic protease B, serotonin and GABA pathways, and immune activation via lipopolysaccharide (LPS). Emerging microbiota-targeted therapeutic strategies, including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), are critically evaluated in light of current evidence from BED and related eating disorders. Despite the promising mechanistic rationale, rigorous clinical trials remain scarce. This review highlights several priorities for future research, and the development of precision medicine strategies integrating established therapeutic approaches with emerging microbiota-targeted interventions.
Vitamin A (VitA) and vitamin E (VitE) deficiencies can result in significant health consequences in children. The role of the intestinal microbiota in these vitamin deficiencies has been scarcely explored. This cross-sectional study aimed to analyze the relationship of VitA depletion and VitE deficiency with metabolic traits, dietary intake, and the gut microbiota composition in 179 school-age children. Serum VitA depletion and VitE deficiency were present in 8.4% and 20.7% of children, respectively. No significant relationship between tocopherol or retinol intake and VitA depletion or VitE deficiency was found. Linear discriminant analysis effect size (LEfSe) and analysis of compositions of microbiomes with bias correction 2 (ANCOM-BC2) analysis revealed no differences in the gut microbiota composition according to VitE status. However, we observed significant enrichment of Veillonella, Haemophilus, and Streptococcus in children with VitA depletion as compared to those with normal VitA levels. The enrichment of these oropharyngeal genera in VitA depletion resembles the gut microbiome composition previously described in childhood stunting. Future functional studies are required to elucidate whether these bacteria play a role in vitamin A metabolism.
Chronic lymphocytic leukemia (CLL) is highly heterogeneous both clinically and biologically. Although genetic factors have been identified, several lines of evidence suggest a role for environmental factors in disease onset and progression. Diet is a recognized risk factor for various diseases, including cancer, with an established relationship to the composition of the gut microbiome. Taking advantage of the widely used Eμ-TCL1 transgenic model, we investigated the relationship between diet, the gut microbiota, and CLL development. We randomized a cohort of Eμ-TCL1 mice to receive a normal standard diet (N) (n = 15) or an experimental diet rich in low-complexity carbohydrates and lower in proteins and fibers (HC/LPF) (n = 16) and observed a progressive shift in microbiome composition in animals fed with the HC/LPF diet, accompanied by an acceleration of disease progression and shortened survival. These effects were associated with an increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes in mice fed with the HC/LPF diet. Our data suggest a close link between the HC/LPF diet and Oscillospira, Ruminococcus, Mucispirillum, AF12, and Rikenella genera, possibly affecting CLL development. The present work paves the way for detailed studies to be conducted in controlled cohorts of patients with CLL to elucidate the role of diet in disease incidence and evolution.
The gut microbiota and microbially produced short chain fatty acids (SCFAs) are increasingly linked to type 2 diabetes (T2D), particularly in the context of dietary transitions from fiber-rich to more ultra-processed foods. Data in African origin populations are lacking. We examined the cross-sectional relationships between the gut microbiota, SCFAs, and T2D by performing amplicon sequencing and targeted metabolomics from fecal samples and measuring fasting glucose, insulin, and C-peptide in 1505 African origin middle-aged adults from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbial diversity and SCFAs were highest among Ghanaian and lowest among US participants. T2D was associated with lower microbial diversity, but not when stratifying by site. Differential abundance analysis (adjusted for site, sex, BMI, and age) identified microbes associated with T2D: Romboutsia was negatively associated with T2D, while positively associated taxa included Escherichia−Shigella sp., Dielma fastidiosa, Klebsiella, and Bacteroides vulgatus. Several species that were differentially abundant by T2D showed strong correlations with SCFA concentrations, although the significance varied by site. Our results suggest that associations between the gut microbiota, SCFAs, and T2D may differ by environmental, dietary, and ecological contexts. Amid the shifting global dietary patterns, further research is needed to inform gut microbiota-targeted approaches to address the global T2D burden.
