ObjectiveThe human gut fungal community, known as the mycobiome, plays a fundamental role in the gut ecosystem and health. Here we aimed to investigate the determinants and long-term stability of gut mycobiome among middle-aged and elderly adults. We further explored the interplay between gut fungi and bacteria on metabolic health.DesignThe present study included 1244 participants from the Guangzhou Nutrition and Health Study. We characterised the long-term stability and determinants of the human gut mycobiome, especially long-term habitual dietary consumption. The comprehensive multiomics analyses were performed to investigate the ecological links between gut bacteria, fungi and faecal metabolome. Finally, we examined whether the interaction between gut bacteria and fungi could modulate the metabolic risk.ResultsThe gut fungal composition was temporally stable and mainly determined by age, long-term habitual diet and host physiological states. Specifically, compared with middle-aged individuals, Blastobotrys and Agaricomycetes spp were depleted, while Malassezia was enriched in the elderly. Dairy consumption was positively associated with Saccharomyces but inversely associated with Candida. Notably, Saccharomycetales spp interacted with gut bacterial diversity to influence insulin resistance. Bidirectional mediation analyses indicated that bacterial function or faecal histidine might causally mediate an impact of Pichia on blood cholesterol.ConclusionWe depict the sociodemographic and dietary determinants of human gut mycobiome in middle-aged and elderly individuals, and further reveal that the gut mycobiome may be closely associated with the host metabolic health through regulating gut bacterial functions and metabolites.

Background Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations. Methods We included 1430 participants from the Guangzhou Nutrition and Health Study (GNHS) with both gut microbiome and cognitive assessment data available as a discovery cohort, of whom 272 individuals provided fecal samples twice before cognitive assessment. We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit. Fecal 16S rRNA and shotgun metagenomic sequencing, targeted serum metabolomics, and cytokine measurements were performed in the GNHS. The validation analyses were conducted in an Alzheimer’s disease case–control study (replication study 1, n = 90) and another community-based cohort (replication study 2, n = 1300) with cross-sectional dataset. Results We found protective associations of specific gut microbial genera (Odoribacter, Butyricimonas, and Bacteroides) with cognitive impairment in both the discovery cohort and the replication study 1. Result of Bacteroides was further validated in the replication study 2. Odoribacter was positively associated with hippocampal volume (β, 0.16; 95% CI 0.06–0.26, P = 0.002), which might be mediated by acetic acids. Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment. We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition. Conclusions Our findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development.

Objective: Previous studies have reported inverse associations between certain healthy lifestyle factors and Non-alcoholic fatty liver disease (NAFLD), but limited evidence showed the synergistic effect of those lifestyles. This study examined the relationship of a combination of lifestyles, expressed as Health Lifestyle Score (HLS), with NAFLD. Design: A community-based cross-sectional study. Questionnaires and body assessments were used to collect data on the 6-item HLS (ranging from 0-6, where higher scores indicate better health). The HLS consists of non-smoking (no active or passive smoking), normal BMI (18.5-23.9 kg/m2), physical activity (moderate or vigorous physical activity ≥ 150 min/week), healthy diet pattern, good sleep (no insomnia or < 6 months), and no anxiety (Self-rating Anxiety Scale < 50), one point each. NAFLD was diagnosed by ultrasonography. Setting: Guangzhou, China. Participants: 2981 participants aged 40-75 years. Results: The overall prevalence of NAFLD was 50.8%. After adjusting for potential covariates, HLS was associated with lower presence of NAFLD. The ORs (95% CI) of NAFLD for subjects with higher HLS (3, 4, 5-6 vs. 0-1 points) were 0.68 (0.51,0.91), 0.58 (0.43,0.78) and 0.35 (0.25,0.51), respectively (P-values < 0.05). Among the 6 items, BMI and physical activity were the strongest contributors. Sensitivity analyses showed that the association was more significant after weighting the HLS. The beneficial association remained after excluding any one of the 6 components or replacing BMI with waist circumference. Conclusion: Higher HLS was associated with lower presence of NAFLD, suggesting that a healthy lifestyle pattern might be beneficial to liver health.

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