Endogenous ethanol (EtOH) production is a newly identified pathophysiological mechanism involved in metabolic dysfunction-associated steatohepatitis (MASH) and liver disease associated with hepatitis B virus (HBV). Therefore, the characterization of EtOH-producing species associated with liver disease could contribute to the development of gut microbiota-targeted approaches. We investigated EtOH production and tolerance, antimicrobial susceptibility and antimicrobial resistance gene(s) in 33 strains isolated in previous culturomics studies and belonging to species enriched in MASH, alcoholic hepatitis (AH) and HBV patients. Enterocloster clostridioformis, Thomasclavelia ramosa and Peptinophilus grossensis were identified as new EtOH-producing species associated with liver diseases. A strong association between EtOH tolerance and production was detected (p < 0.05). Yeast, Enterocloster species (strictly anaerobic bacteria) and Limosilactobacillus fermentum produced the highest concentrations of EtOH (0.8 to 3.3 g/L). The poorly absorbed drugs, amphotericin B, rifaximin and vancomycin together showed high in vitro susceptibility. Furthermore, E. clostridioformis EC38 harbored the vanB operon. New EtOH-producing species associated with liver diseases were identified thanks to culturomics. Notably, most of them are anaerobic bacteria. These findings underscore the need to further investigate anaerobic gut microbiota species enriched in liver diseases with the aim of developing gut microbiota-targeted therapies.
Emerging evidence supports a bidirectional relationship between the gut microbiome and sleep, which is partly mediated by the microbiota‒gut‒brain axis. Infancy is a critical window for the establishment of both the gut microbiome and sleep regulation, which we hypothesize to be linked across both short (diurnal) and long (monthly) time scales. In this longitudinal study, we investigated associations between gut microbiota development and sleep patterns in 20 infants at 2, 4, and 6 months of age (n = 163 samples). Infants were continuously monitored across 48-h sampling periods. The gut microbiota profiles were characterized using 16S rRNA gene sequencing; gut melatonin concentrations were measured; sleep data were collected via wearable actimetry, 24-h parent-reported sleep diaries, and the Brief Infant Sleep Questionnaire; and parenting style and behavioral development were assessed. In some infants, bacterial diversity followed diurnal rhythmic patterns. While bacterial rhythmicity was not significantly associated with sleep rhythmicity, infants with higher microbial alpha diversity showed more robust sleep patterns. Infant age emerged as the strongest predictor of gut microbial diversity and melatonin levels. Our findings suggest that gut microbial establishment may support the maturation of sleep‒wake rhythms in early infancy. Further research is needed to elucidate mechanistic roles of the gut microbiome in sleep development.
The human gut microbiome, a diverse community of trillions of microorganisms, is essential for controlling numerous bodily functions, such as metabolism, immune response, and epithelial barrier integrity. The gut microbiota comprises bacteria, viruses, fungi, and other microorganisms that affect human health, metabolic pathways, and immune responses. Dysbiosis, or the imbalance of gut microbial composition, has been linked to the pathogenesis of several ailments, including cardiovascular conditions, gastrointestinal conditions, allergies, obesity, autoimmune disorders, and tumors. The interaction between gut microbes and immune responses, mainly through Tregs cells and Th17 cells, underscores the microbiome's function in immune regulation. Furthermore, gut microbial metabolites act as signaling molecules and substrates for metabolic processes, impacting autoimmune disorders and cancer development. Recent research highlights the microbiome's potential role in cancer immunoediting, where gut microbial metabolites may either promote or suppress cancer progression by modulating inflammation and immunosuppression. This review delves into the critical functions of the gut microbiome, its influence on autoimmune disorders, and the emerging connection between gut microbial metabolites and cancer immunoediting, offering new insights into their impact on human health and disease.
Obesity in older adults is a known risk factor for Alzheimer's disease and related dementias, potentially driven by metabolic dysfunction, inflammation and gut dysbiosis. The gut-brain axis, influenced by diet and the gut microbiome, is increasingly recognized as a contributor to neurodegeneration. In this sub-analysis of a 10-week randomized dietary education intervention (NCT06121986), we examined how obesity modulates gut microbiome, metabolome, and cognitive responses in 31 adults aged 55-85, with or without mild cognitive impairment. Participants received education on either a Mediterranean Diet or a Modified Mediterranean-Ketogenic Diet. Analyses were stratified by baseline obesity (BMI ≥30 kg/m²). Individuals with obesity exhibited lower microbial alpha-diversity, higher Bacteroides, and lower Akkermansia and Christensenellaceae_R-7_group, along with poorer memory and executive function. Only in the obese group did fat loss correlate with improvements in episodic memory and cognitive flexibility. In contrast, increased fat mass was associated with improved memory in non-obese participants. Gains in skeletal muscle mass predicted cognitive improvement in adults aged ≥73. Changes in gut (acetate, propionate, lactate) and plasma (acetate, pyruvate, citric acid) metabolites were linked to cognitive and body composition outcomes. These exploratory findings highlight the gut-muscle-brain axis as a modifiable target to enhance cognitive health in aging populations.
Lung cancer continues to claim countless lives globally. Several studies have shown that the gut microbiome is vital in maintaining healthy lung function through the gut-lung axis. A comparison between the gut microflora of healthy volunteers and lung cancer patients revealed that changes in the composition of gut microflora occur in lung cancer patients. The gut microflora may contribute to lung cancer by influencing immune reactions, inflammatory pathways, bacterial metabolites modulating host metabolism, microbiome dysbiosis, genotoxicity, virulence, and bacteria-induced epigenetic alterations. Thus, it may be assumed that maintaining a healthy gut microflora could help prevent lung cancer. Nutraceuticals are specialized products designed to support health and address specific nutritional needs. They contain ingredients like vitamins, minerals, probiotics, polyphenols, and herbs to reduce the risk or impact of certain illnesses. Nutraceuticals, including probiotics and polyphenols, play a role in preventing and treating various cancers, including lung cancer, by modulating the gut microbiome. This review examines the link between the gut microbiome and lung cancer, how it contributes to cancer development, and the impact of dietary interventions - particularly probiotics, polyphenols, and dietary fibers - on lung cancer prevention and treatment.
The rapid spread of antimicrobial-resistant (AMR) bacteria is a major global health challenge. The misuse of antibiotics and infections by resistant pathogens drive the dissemination of resistance genes, the human microbiota of which serve as reservoirs. Disruptions in the host-microbiota balance, which are influenced by diet, can increase resistance genes. Low-fiber diets are linked to gut dysbiosis, infection susceptibility, and weakened defenses. Here, we report that dietary fiber deprivation induced significant alterations in the gut microbiota of C57BL/6 mice, leading to reduced host tolerance to lung infection by the AMR strain Klebsiella pneumoniae B31 (KP 31) with higher levels of ampicillin-resistant Enterobacteriaceae and marked shifts in the gut microbial composition. Germ-free mice that received fecal transplants from fiber-deprived donors also displayed exacerbated inflammatory pathology following KP 31 infection. Infection further increased the abundance of cultivable resistant Enterobacteriaceae in the gut and was associated with the modulation of short-chain fatty acid (SCFA) levels, particularly propionate. Propionate appears to support antimicrobial activity, and its decrease in vitro promotes bacterial growth. Our findings highlight that the gut microbiota is a crucial reservoir for resistance genes. Low-fiber diets impair lung defenses and promote resistome expansion after AMR infection. Understanding these dynamics and their influencing factors is essential for strategies to combat antimicrobial resistance (AMR).
The human gut microbiota is central to the health and development of the host, and the early-life microbiota is affected by a range of factors that can alter the infant's development for years to come. The role of the external, natural environment in shaping the gut microbiota is still largely unknown. We examined how the environment surrounding the home postnatally is associated with the infant gut microbiota in the first 2 y of life. The study utilized 16 s rRNA data from 893 children's fecal samples from the longitudinal birth cohort HELMi. We show that the environment has a minimal overall association with microbiota development (R2 < 1%). Air quality explained the greatest degree of variation in microbiota composition, while only forests, agriculture and inland wetlands near the home had any significant association with bacterial genera. The results suggest that the infant gut microbiota is not strongly dependent on the external natural environment, and that the impact of the environment is mostly due to exposure to air pollution that may affect the host's immune system and indirectly the gut microbiota.
Posttraumatic stress disorder (PTSD), depression, and anxiety disorders are prevalent and often overlapping mental health conditions with complex, multifactorial etiologies. Growing evidence implicates the gut microbiome in their pathophysiology through immune modulation, neurotransmitter regulation, and bidirectional gut-brain signaling. Findings remain fragmented and difficult to reconcile due to differences in study populations, clinical contexts, and analytic methods. This structured narrative review synthesizes current evidence on gut microbial alterations in PTSD, depression, and anxiety, while examining methodological sources of heterogeneity. We searched four databases: PubMed, Scopus, Web of Science, and PsycINFO, and identified 64 eligible studies assessing the gut microbiome composition in these disorders. Sample sizes ranged from small, exploratory cohorts (≈20 participants) to large population-based datasets (>1000 participants), with most studies conducted in China. Stool sampling and DNA extraction protocols varied widely, although 16S rRNA gene amplicon sequencing of the V3-V4 region on Illumina platforms predominated. Alpha-diversity results were inconsistent, whereas beta-diversity analyses distinguished cases from controls. Across these disorders, alterations in microbial composition was observed, including enrichment of proinflammatory and depletion of beneficial bacterial taxa. The current findings indicate that that the gut microbiome represents a promising avenue for biomarker discovery and therapeutic innovation.
Gut microbial turnover in humans remains poorly understood. We evaluated gut bacterial viability by quantifying viable cells and relating them to indicators of gut environmental status. Fecal microbial loads (microbial cells per gram feces) were quantified by flow cytometry using the DNA-intercalating dye SytoBC, and viable bacteria were identified by fluorescence in situ hybridization with the 16S rRNA-targeted Eub338 probe. Bacteria retaining sufficient rRNA were defined as viable, and the living bacterial rate was calculated as the proportion of Eub338-positive cells among SytoBC-positive cells. These metrics were applied to starvation‑cultured gut bacterial strains and fecal samples from patients with ulcerative colitis (UC), older adults, and healthy individuals. Starvation culture showed time‑dependent decreases in living bacterial rate and viable cell counts, consistent with colony-forming unit measurements. Patients with active UC exhibited reduced fecal microbial loads and viable microbial loads. Living bacterial rates negatively correlated with fecal calprotectin and Mayo score. In older adults, reduced living bacterial rates and viable Bifidobacteriaceae were associated with higher fecal calprotectin. In healthy individuals, lower living bacterial rates and viable Lachnospiraceae were associated with harder stools and reduced defecation frequency. Quantitative profiling of viable fecal bacteria may aid in characterizing intestinal homeostasis and dysbiosis‑associated conditions.
The positive effects of dietary flavonoids on health depend on their bioavailability in the human gut, where the flavonoid-modifying enzymes (FMEs) in gut bacteria play a crucial role in flavonoid metabolism. Thus, to comprehensively examine the role of FMEs in this process, we first constructed a database of potential FMEs containing 6,865 proteins. We identified homologs of these FMEs in gut bacterial genomes and reported species that can potentially modify flavonoids but were not previously known in this context. We examined the differential abundance of FMEs in the gut microbiomes of healthy and diseased individuals from Western and non-Western populations with distinct dietary habits. The differential enrichment of key FMEs between Western and non-Western populations and between disease and healthy samples highlights differences in gut flavonoid metabolism based on diet, population, and health status. This study reveals a comprehensive landscape of flavonoid metabolism in the human gut microbiome.
Physical activity (PA) has been suggested to influence the gut microbiome. We evaluated this association among low-income Black American adults. This study included 489 self-identified Black American participants from the Southern Community Cohort Study. PA data, including exercise/sport- and work/home-related moderate-vigorous PA (MVPA), was collected at cohort enrollment (2002-2009). Stool samples were collected between 2018 and 2021, and microbial composition was profiled using shotgun metagenomic sequencing. General linear regression models were employed to evaluate associations between PA and gut microbial α-diversity, abundance of individual species and metabolic pathways. Among all participants, MVPA measures were not associated with Shannon α-diversity (p > 0.05) and explained approximately 0.2-0.3% variation of Bray-Curtis dissimilarity. A total of 32 bacterial species, including seven Bacteroides species, two Streptococcus species, two Prevotella species, and nine microbial metabolic pathways, including D-fucofuranose biosynthesis, xyloglucan degradation, biosynthesis of L-citrulline, L-aspartate and L-asparagine biosynthesis, and urea cycle, were significantly associated with work/home-related and/or total MVPA (all false discovery rates < 0.10). In conclusion, MVPA, particularly from work and home activities, may modulate the composition and functionality of the gut microbiome among Black American adults. Work/home-related moderate-vigorous physical activity (MVPA_w) and/or total MVPA (MVPA_a) comprising of MVPA_w and exercise/sport-related MVPA (MVPA_s) are associated with abundance of 32 gut bacterial species in Black American adults.MVPA_w and/or MVPA_a are associated with nine gut metabolic pathways.
There is inconsistency in the evidence regarding the effects of food on the gut microbiome. These inconsistencies arise, in part, from substantial inter- and intraindividual variations in diet. The wide range of foods consumed directly influences substrate availability for the microbiota. By categorizing foods into broad groups and overlooking interactions among food constituents within individual foods, current dietary pattern approaches can obscure food-specific differences needed to understand dietary effects. Differences in habitual and occasional intake further complicate analyses since frequency of food consumption can produce different gut microbiota responses within the same individual. Flexible analytical approaches are needed to capture within-individual food intake frequency and food-specific effects. To address these challenges, this narrative review presents dietary pattern concepts that distinguish static (stable or consistent) and dynamic (fluctuating or episodic) intake of specific foods at the individual level. We performed a literature search in three databases, including Medline, CINAHL, and PsycINFO, to retrieve relevant articles that distinguish the concepts of "core foods" and "secondary foods" in population-level studies. We adapt these concepts to a microbiome context at the individual level and propose future directions for studies investigating the impact of diet on the gut microbiome.
HIV-infected immunological nonresponders (INRs) endure persistent T-cell dysfunction and chronic inflammation, facing high risk of various complications and mortality, with no effective therapies available. Silybin, the principal constituent of a plant extract, possesses anti-inflammation and immunomodulatory properties. The gut microbiome has been shown to modulate the efficacy of immune therapies and drugs. We gave 54 INRs oral silybin for three months and used multi-omics to investigate the gut-related factors influencing the efficacy of silybin. Silybin raised CD4+ T cells counts in 52% of participants and an efficacy classification model based on baseline gut microbiome and metabolites was developed. Favorable gut bacteria produced anti-inflammatory metabolites that downregulated Ras/MAPK/PI3K-Akt signaling pathways also targeted by silybin. Our findings shed light on a novel therapeutic approach for addressing immune dysfunction in HIV-positive INRs and have important implications for personalized medical strategies in the management of HIV infection.
Preclinical studies have implicated the microbiota in body weight control, but its translation to humans remains uncertain, partly owing to methodological variability in assessing the relationship between diet-induced obesity and microbiota composition. We performed an internal meta-analysis to determine whether the propensity for diet-induced obesity, defined by relative weight gain due to a high-fat, high-sugar "cafeteria" diet, is associated with changes in microbiota composition. We collated fecal microbiome data from 12 studies using our validated model of diet-induced obesity (208 male and 74 female Sprague-Dawley rats; 3.5-13 weeks of chow (control) or cafeteria diet) and determined whether the alpha diversity and composition of the gut microbiota differed between obese-prone and obese-resistant rats. We found consistent effects of cafeteria diet exposure on the microbiota, with marked changes in overall composition, and reduced microbial richness and evenness. Furthermore, specific obesity-associated microbial genera, such as Bacteroides and Blautia, were enriched by the cafeteria diet. Critically, alpha diversity measures and the gut microbiota composition did not differ between obese-prone and obese-resistant rats in either diet group. Our findings suggest that while the microbiota is substantially altered by cafeteria diet intake, these changes appear unrelated to individual susceptibility to weight gain, highlighting the role of additional host factors in modulating diet-induced obesity.
Dietary fiber and fat shape the gut microbiota and human health, yet their role in modulating the response of the microbiota to antibiotics remains underexplored. We hypothesized that dietary fiber, independent of fat content, mitigates antibiotic-induced weight loss and diarrhea in a microbiota-dependent manner. Mice were fed refined diets varying in fat and fiber contents for 6 weeks, compared to a standard plant-based chow diet. Following antibiotic administration, fiber consumption independent of fat reduced diarrhea and weight loss. High-fiber diets increased Bacteroidetes and decreased Firmicutes and Proteobacteria prior to antibiotic exposure, all of which correlated with elevated cecal short-chain fatty acids (SCFAs). Fermentable fiber increased AI-2 quorum-sensing pathway activity and improved Firmicutes resiliency to antibiotics. Supplementation with AI-2 reduced antibiotic-induced weight loss in mice fed high-fat, low-fiber diets. These findings suggest that fermentable fiber alters the gut microbiota composition and function, enhancing microbial resiliency and host tolerance to antibiotics. Dietary supplementation with microbiota-accessible fiber increased AI-2 production, stabilized Firmicutes populations, and attenuated antibiotic-associated weight loss, independent of dietary fat content.
Methanogens are methane-producing archaea that are present in the human gut. Yet, their adaptation to diverse human lifestyles remains poorly understood. Here, we report the isolation of Methanobrevibacter intestini G0370_i3 from the stool of a healthy adult from Southern Gabon, Africa, where inhabitants maintain traditional subsistence lifestyles with diets distinct from industrialized populations. M. intestini was enriched from human stool, phenotypically characterized, and sequenced. G0370_i3 growth relied on the presence of H2 and CO2 and could also grow on formate, in contrast to reports for the type strain. The genome encoded pathways for amino acid biosynthesis, cofactor metabolism, and secondary metabolite production. We identified 23 mobile genetic elements and five defense systems, indicating horizontal gene transfer and antiviral defense. No prophage regions were detected.The genome also encoded uridine diphosphate (UDP)-sugar metabolism pathways, indicating capacity for energy storage and cell wall adaptability. Genes encoding adhesin-like proteins suggest capabilities for host interaction. Phenotypically, G0370_i3 is a coccobacillus, grows optimally at 37°C, and tolerates antibiotics, salt, and oxygen stress. These findings highlight the stress resilience and selective metabolic capabilities of M. intestini and underscore the importance of representing African populations in microbiome research.
Gut microbial metabolism is intimately coupled to host health and disease. Recent knowledge on potential health benefits of gut microbiome lays the groundwork for development of novel therapeutic strategies. But how microbiota-derived metabolites impact on host-microbiome crosstalk remains untapped from therapeutic perspectives. In this study, six gut bacteria sourced from a fecal pool of forty healthy donors were cultured in three distinct growth media. Subsequently, the bacteria were identified through 16S rRNA gene sequencing and subjected to metabolite extraction to evaluate their anti-microbial, anti-oxidant and anti-thrombotic potential. Findings reveal strong anti-oxidant activities in the metabolic-extracts from all the isolates. Metabolites derived from Lactobacillus rhamnosus, Priestia flexa and Bacillus subtiilis inhibited the growth of clinically pathogenic strains Escherichia coli ATCC-8739, Salmonella typhi ATCC-1408 and Staphylococcus aureus ATCC-6538. Escherichia fergusonii originated metabolites demonstrated the highest efficacy in lysing blood clots compared to streptokinase. Additionally, extracts from all the isolates exhibited significant ability to delay coagulation time, competing with standard warfarin. Thus, the findings of our early-stage study provide novel insights into metabolomic functions of gut microbiota. This study underscores the significance of exploring these active metabolites for prospective therapeutic and clinical exploration at the intersection of drug discovery and live bio-therapeutics.
In recent years, understanding the intricate connection between gut microbiome and cancer development has gained significant attention. The gut microbiome has a key role in maintaining overall human health and modulating the body's defense mechanism against various diseases. This review examines the multifaceted association between the gut microbiome and breast cancer, providing a comprehensive overview of studies from the last two decades that investigate both anti-cancer and pro-cancer properties of gut metabolites. Compounds such as nisin, inosine, acetate, propionate, and conjugated linoleic acids have demonstrated potential as therapeutic agents against breast cancer, while others, including butyrate, lactate, certain bile acids, and secondary metabolites, exhibit dual roles, showing both anti-cancer and pro-cancer properties under different conditions, with some implicated in tumor progression. Moreover, emerging research highlights the dual roles of these metabolites in influencing the efficacy of conventional breast cancer therapies. Despite promising evidence, the molecular mechanisms underlying these opposing actions remain unclear and require further investigation. To advance our understanding, future research should prioritize elucidating these mechanisms, establishing dose-response relationships, and conducting animal and clinical studies to validate in vitro findings. This review also identifies key gaps and highlights potential directions for future research in this field.
Underlying mechanisms by which exposures to toxic metals/metalloids impact obesity and type 2 diabetes (T2DM) risk remain largely unknown. Gut microbiota have been strongly associated with cardiometabolic risk. To assess relationships between high metal exposures, gut dysbiosis, and metabolic dysregulation, we analyzed associations among gut microbiome taxa, dichotomized metal levels (arsenic, lead, mercury, cadmium), clinical measures (BMI, fasting blood glucose, blood pressure), and diagnoses (hypertension, obesity, diabetes) in 178 African-origin adults (52% female, mean age = 43.0 ± 6.4 years) from Ghana, South Africa, Jamaica, Seychelles, and USA. High vs. low lead and arsenic levels had a significant effect on beta diversity (p < 0.05). Seventy-one taxa were associated with high lead levels: 30 with elevated BMI, 22 with T2DM, and 23 with elevated fasting blood glucose (p < 0.05); 115 taxa were associated with high arsenic levels: 32 with elevated BMI, 33 with T2DM, and 26 with elevated blood glucose (p < 0.05). Porphyrin metabolism was the most enriched metabolic pathway in taxa associated with higher lead and arsenic exposure. These data provide the first findings from African-origin adults that demonstrate the association between the gut microbiome with lead and arsenic exposure and obesity and T2DM risk.
Approximately 70% of all pregnancies are affected by nausea and vomiting (NVP), yet the mechanisms controlling this phenomenon are not well known. Pregnancy hormones explain a large part of this effect, mostly through human chorionic gonadotropin and fetal production of GDF15, a hormone active in the brain stem. Still, there is a wide variation in the severity of symptoms, ranging from no nausea to severe vomiting requiring hospitalization (hyperemesis gravidarum). Here, we present a nested case‒control study within the large SweMaMi cohort, wherein 337 participants with severe NVP in early pregnancy were matched 1-to-1 with moderate and mild NVP, respectively. Subjects with more severe nausea had lower richness and diversity in their fecal microbiomes. Several taxa were significantly associated with NVP score, where the most extreme are a negative correlation with Lactobacillaceae and positive correlations with Bifidobacterium dentium and Puniceicoccaceae. Finally, higher NVP score was associated with a higher abundance of bacteria encoding for the neuroactive pathways of glutamine degradation, inositol synthesis, and lactate production. In conclusion, the gut microbiota was strongly associated with NVP. Further studies with direct interventions capable of restoring the early-pregnancy gut microbiome could open up new approaches for dealing with the most common symptom of early pregnancy.