Objectives To investigate the association between intake of fish and n-3 polyunsaturated fatty acids (n-3 PUFA) and the risk of breast cancer and to evaluate the potential dose-response relation. Design Meta-analysis and systematic review of prospective cohort studies. Data sources PubMed and Embase up to December 2012 and references of retrieved relevant articles. Eligibility criteria for selecting studies Prospective cohort studies with relative risk and 95% confidence intervals for breast cancer according to fish intake, n-3 PUFA intake, or tissue biomarkers. Results Twenty six publications, including 20 905 cases of breast cancer and 883 585 participants from 21 independent prospective cohort studies were eligible. Eleven articles (13 323 breast cancer events and 687 770 participants) investigated fish intake, 17 articles investigated marine n-3 PUFA (16 178 breast cancer events and 527 392 participants), and 12 articles investigated alpha linolenic acid (14 284 breast cancer events and 405 592 participants). Marine n-3 PUFA was associated with 14% reduction of risk of breast cancer (relative risk for highest v lowest category 0.86 (95% confidence interval 0.78 to 0.94), I²=54), and the relative risk remained similar whether marine n-3 PUFA was measured as dietary intake (0.85, 0.76 to 0.96, I²=67%) or as tissue biomarkers (0.86, 0.71 to 1.03, I²=8%). Subgroup analyses also indicated that the inverse association between marine n-3 PUFA and risk was more evident in studies that did not adjust for body mass index (BMI) (0.74, 0.64 to 0.86, I²=0) than in studies that did adjust for BMI (0.90, 0.80 to 1.01, I²=63.2%). Dose-response analysis indicated that risk of breast cancer was reduced by 5% per 0.1g/day (0.95, 0.90 to 1.00, I²=52%) or 0.1% energy/day (0.95, 0.90 to 1.00, I²=79%) increment of dietary marine n-3 PUFA intake. No significant association was observed for fish intake or exposure to alpha linolenic acid. Conclusions Higher consumption of dietary marine n-3 PUFA is associated with a lower risk of breast cancer. The associations of fish and alpha linolenic acid intake with risk warrant further investigation of prospective cohort studies. These findings could have public health implications with regard to prevention of breast cancer through dietary and lifestyle interventions.

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 To identify the core gut microbial features associated with type 2 diabetes risk and potential demographic, adiposity, and dietary factors associated with these features. RESEARCH DESIGN AND METHODS We used an interpretable machine learning framework to identify the type 2 diabetes–related gut microbiome features in the cross-sectional analyses of three Chinese cohorts: one discovery cohort (n = 1,832, 270 cases of type 2 diabetes) and two validation cohorts (cohort 1: n = 203, 48 cases; cohort 2: n = 7,009, 608 cases). We constructed a microbiome risk score (MRS) with the identified features. We examined the prospective association of the MRS with glucose increment in 249 participants without type 2 diabetes and assessed the correlation between the MRS and host blood metabolites (n = 1,016). We transferred human fecal samples with different MRS levels to germ-free mice to confirm the MRS–type 2 diabetes relationship. We then examined the prospective association of demographic, adiposity, and dietary factors with the MRS (n = 1,832). RESULTS The MRS (including 14 microbial features) consistently associated with type 2 diabetes, with risk ratio for per 1-unit change in MRS 1.28 (95% CI 1.23–1.33), 1.23 (1.13–1.34), and 1.12 (1.06–1.18) across three cohorts. The MRS was positively associated with future glucose increment (P < 0.05) and was correlated with a variety of gut microbiota–derived blood metabolites. Animal study further confirmed the MRS–type 2 diabetes relationship. Body fat distribution was found to be a key factor modulating the gut microbiome–type 2 diabetes relationship. CONCLUSIONS Our results reveal a core set of gut microbiome features associated with type 2 diabetes risk and future glucose increment.

Objective: The 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. Design: The 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. Results: The 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. Conclusion: We 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.

Evidence from human cohorts indicates that chronic insomnia is associated with higher risk of cardiometabolic diseases (CMD), yet whether gut microbiota plays a role is unclear. Here, in a longitudinal cohort (n = 1809), we find that the gut microbiota-bile acid axis may link the positive association between chronic insomnia and CMD. Ruminococcaceae UCG-002 and Ruminococcaceae UCG-003 are the main genera mediating the positive association between chronic insomnia and CMD. These results are also observed in an independent cross-sectional cohort (n = 6122). The inverse associations between those gut microbial biomarkers and CMD are mediated by certain bile acids (isolithocholic acid, muro cholic acid and nor cholic acid). Habitual tea consumption is prospectively associated with the identified gut microbiota and bile acids in an opposite direction compared with chronic insomnia. Our work suggests that microbiota-bile acid axis may be a potential intervention target for reducing the impact of chronic insomnia on cardiometabolic health.

Background: Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear.Results: This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested thatDesulfovibrionaceaeandOdoribacterhad significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found thatSaccharibacteriacould potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance ofBurkholderialesandAlcaligenaceaeand decreased the abundance ofLachnobacterium,Bacteroides coprophilus,Barnesiellaceae, an undefined genus in the familyVeillonellaceaeandMitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features.Conclusions: These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans.