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OBJECTIVE: The remodelling of gut mycobiome (ie, fungi) during pregnancy and its potential influence on host metabolism and pregnancy health remains largely unexplored. Here, we aim to examine the characteristics of gut fungi in pregnant women, and reveal the associations between gut mycobiome, host metabolome and pregnancy health. DESIGN: Based on a prospective birth cohort in central China (2017 to 2020): Tongji-Huaxi-Shuangliu Birth Cohort, we included 4800 participants who had available ITS2 sequencing data, dietary information and clinical records during their pregnancy. Additionally, we established a subcohort of 1059 participants, which included 514 women who gave birth to preterm, low birthweight or macrosomia infants, as well as 545 randomly selected controls. In this subcohort, a total of 750, 748 and 709 participants had ITS2 sequencing data, 16S sequencing data and serum metabolome data available, respectively, across all trimesters. RESULTS: The composition of gut fungi changes dramatically from early to late pregnancy, exhibiting a greater degree of variability and individuality compared with changes observed in gut bacteria. The multiomics data provide a landscape of the networks among gut mycobiome, biological functionality, serum metabolites and pregnancy health, pinpointing the link between Mucor and adverse pregnancy outcomes. The prepregnancy overweight status is a key factor influencing both gut mycobiome compositional alteration and the pattern of metabolic remodelling during pregnancy. CONCLUSION: This study provides a landscape of gut mycobiome dynamics during pregnancy and its relationship with host metabolism and pregnancy health, which lays the foundation of the future gut mycobiome investigation for healthy pregnancy.
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Microbioma Gastrointestinal , Micobioma , Humanos , Femenino , Embarazo , Microbioma Gastrointestinal/fisiología , Adulto , Estudios Prospectivos , China , Metaboloma , Hongos/aislamiento & purificación , Recién NacidoRESUMEN
SCOPE: Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits. METHODS AND RESULTS: The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels. CONCLUSION: Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health.
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Diabetes Gestacional , Microbioma Gastrointestinal , Vitamina D , Humanos , Femenino , Diabetes Gestacional/microbiología , Diabetes Gestacional/sangre , Embarazo , Vitamina D/sangre , Vitamina D/análogos & derivados , Estudios Transversales , Microbioma Gastrointestinal/fisiología , Adulto , Estudios Prospectivos , Glucemia/metabolismoRESUMEN
Background: The escalating prevalence of hyperuricemia is emerging as a significant public health concern. The association between dietary lignans and hyperuricemia is yet to be fully elucidated. Our study aims to evaluate the relationships between dietary lignan intake and hyperuricemia among middle-aged and elderly Chinese individuals, with an additional focus on investigating the underlying mechanisms. Methods: Dietary lignan intake was measured using a validated Food Frequency Questionnaire in 3801 participants at the baseline. Among them, 2552 participants were included in the longitudinal study with a median follow-up of 10.5 years. The gut microbiota was analyzed by shotgun metagenome sequencing in 1789 participants, and the targeted fecal metabolome was determined in 987 participants using UPLC-MS/MS at the midpoint of follow-up. Results: The multivariable-adjusted HRs (95% CIs) for hyperuricemia incidence in the highest quartile (vs. the lowest quartile) of dietary intake of total lignans, matairesinol, pinoresinol, and secoisolariciresinol were 0.93 (0.78-1.10), 0.77 (0.66-0.90), 0.83 (0.70-0.97), and 0.85 (0.73-1.00), respectively. The gut microbial and fecal metabolic compositions were significantly different across the dietary lignan groups and the hyperuricemia groups. The beneficial associations between dietary lignans and hyperuricemia might be mediated by several gut microbes (e.g., Fusobacterium mortiferum and Blautia sp. CAG-257) and the downstream bile acid products (e.g., NorCA, glycochenodeoxycholic acid, and glycoursodeoxycholic acid). Conclusion: We found that dietary lignans were inversely associated with hyperuricemia incidence, and the gut microbiota-bile acid axis might mediate this association. Our findings provide new perspectives on precise therapeutic targets and underlying mechanisms for conditions associated with elevated uric acid.
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Ácidos y Sales Biliares , Microbioma Gastrointestinal , Hiperuricemia , Lignanos , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Lignanos/administración & dosificación , Persona de Mediana Edad , Masculino , Femenino , Estudios Prospectivos , Anciano , Ácidos y Sales Biliares/metabolismo , Estudios Longitudinales , Heces/microbiología , Dieta , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , China , AdultoAsunto(s)
Encéfalo , Proteoma , Proteoma/genética , Encéfalo/metabolismo , Animales , Mapeo Cromosómico , Humanos , RatonesRESUMEN
Since dietary intake is challenging to directly measure in large-scale cohort studies, we often rely on self-reported instruments (e.g., food frequency questionnaires, 24-hour recalls, and diet records) developed in nutritional epidemiology. Those self-reported instruments are prone to measurement errors, which can lead to inaccuracies in the calculation of nutrient profiles. Currently, few computational methods exist to address this problem. In the present study, we introduce a deep-learning approach --- Microbiome-based nutrient profile corrector (METRIC), which leverages gut microbial compositions to correct random errors in self-reported dietary assessments using 24-hour recalls or diet records. We demonstrate the excellent performance of METRIC in minimizing the simulated random errors, particularly for nutrients metabolized by gut bacteria in both synthetic and three real-world datasets. Further research is warranted to examine the utility of METRIC to correct actual measurement errors in self-reported dietary assessment instruments.
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The role of circulatory proteomics in osteoporosis is unclear. Proteome-wide profiling holds the potential to offer mechanistic insights into osteoporosis. Serum proteome with 413 proteins was profiled by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, and the 2nd, and 3rd follow-ups (7704 person-tests) in the prospective Chinese cohorts with 9.8 follow-up years: discovery cohort (n = 1785) and internal validation cohort (n = 1630). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) at follow-ups 1 through 3 at lumbar spine (LS) and femoral neck (FN). We used the Light Gradient Boosting Machine (LightGBM) to identify the osteoporosis (OP)-related proteomic features. The relationships between serum proteins and BMD in the two cohorts were estimated by linear mixed-effects model (LMM). Meta-analysis was then performed to explore the combined associations. We identified 53 proteins associated with osteoporosis using LightGBM, and a meta-analysis showed that 22 of these proteins illuminated a significant correlation with BMD (p < 0.05). The most common proteins among them were PHLD, SAMP, PEDF, HPTR, APOA1, SHBG, CO6, A2MG, CBPN, RAIN APOD, and THBG. The identified proteins were used to generate the biological age (BA) of bone. Each 1 SD-year increase in KDM-Proage was associated with higher risk of LS-OP (hazard ratio [HR], 1.25; 95% CI, 1.14-1.36, p = 4.96 × 10-06 ), and FN-OP (HR, 1.13; 95% CI, 1.02-1.23, p = 9.71 × 10-03 ). The findings uncovered that the apolipoproteins, zymoproteins, complements, and binding proteins presented new mechanistic insights into osteoporosis. Serum proteomics could be a crucial indicator for evaluating bone aging.
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Osteoporosis , Proteoma , Humanos , Estudios Prospectivos , Proteómica , Cromatografía Liquida , Espectrometría de Masas en Tándem , Osteoporosis/genética , EnvejecimientoRESUMEN
Background: Continuous glucose monitoring (CGM) has shown potential in improving maternal and neonatal outcomes in individuals with type 1/2 diabetes, but data in gestational diabetes mellitus (GDM) is limited. We aimed to explore the relationship between CGM-derived metrics during pregnancy and pregnancy outcomes among women with GDM. Methods: We recruited 1302 pregnant women with GDM at a mean gestational age of 26.0 weeks and followed them until delivery. Participants underwent a 14-day CGM measurement upon recruitment. The primary outcome was any adverse pregnancy outcome, defined as having at least one of the outcomes: preterm birth, large-for-gestational-age (LGA) birth, fetal distress, premature rupture of membranes, and neonatal intensive care unit (NICU) admission. The individual outcomes included in the primary outcome were considered as secondary outcomes. We conducted multivariable logistic regression to evaluate the association of CGM-derived metrics with these outcomes. Findings: Per 1-SD difference in time above range (TAR), glucose area under the curve (AUC), nighttime mean blood glucose (MBG), daytime MBG, and daily MBG was associated with higher risk of any adverse pregnancy outcome, with odds ratio: 1.22 (95% CI 1.08-1.36), 1.22 (95% CI 1.09-1.37), 1.18 (95% CI 1.05-1.32), 1.21 (95% CI 1.07-1.35), and 1.22 (95% CI 1.09-1.37), respectively. Time in range, TAR, AUC, nighttime MBG, daytime MBG, daily MBG, and mean amplitude of glucose excursions were positively associated, while time blow range was inversely associated with the risk of LGA. Additionally, higher value for TAR was associated with higher risk of NICU admission. We further summarized the potential thresholds of TAR (2.5%) and daily MBG (4.8 mmol/L) to distinguish individuals with and without any adverse pregnancy outcome. Interpretation: The CGM-derived metrics may help identify individuals at higher risk of adverse pregnancy outcomes. These CGM biomarkers could serve as potential new intervention targets to maintain a healthy pregnancy status among women with GDM. Funding: National Key R&D Program of China, National Natural Science Foundation of China, and Westlake Laboratory of Life Sciences and Biomedicine.
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BACKGROUND: The early life stage is critical for the gut microbiota establishment and development. We aimed to investigate the lifelong impact of famine exposure during early life on the adult gut microbial ecosystem and examine the association of famine-induced disturbance in gut microbiota with type 2 diabetes. METHODS: We profiled the gut microbial composition among 11,513 adults (18-97 years) from three independent cohorts and examined the association of famine exposure during early life with alterations of adult gut microbial diversity and composition. We performed co-abundance network analyses to identify keystone taxa in the three cohorts and constructed an index with the shared keystone taxa across the three cohorts. Among each cohort, we used linear regression to examine the association of famine exposure during early life with the keystone taxa index and assessed the correlation between the keystone taxa index and type 2 diabetes using logistic regression adjusted for potential confounders. We combined the effect estimates from the three cohorts using random-effects meta-analysis. RESULTS: Compared with the no-exposed control group (born during 1962-1964), participants who were exposed to the famine during the first 1000 days of life (born in 1959) had consistently lower gut microbial alpha diversity and alterations in the gut microbial community during adulthood across the three cohorts. Compared with the no-exposed control group, participants who were exposed to famine during the first 1000 days of life were associated with consistently lower levels of keystone taxa index in the three cohorts (pooled beta - 0.29, 95% CI - 0.43, - 0.15). Per 1-standard deviation increment in the keystone taxa index was associated with a 13% lower risk of type 2 diabetes (pooled odds ratio 0.87, 95% CI 0.80, 0.93), with consistent results across three individual cohorts. CONCLUSIONS: These findings reveal a potential role of the gut microbiota in the developmental origins of health and disease (DOHaD) hypothesis, deepening our understanding about the etiology of type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Efectos Tardíos de la Exposición Prenatal , Inanición , Adulto , Humanos , Persona de Mediana Edad , China , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Pueblos del Este de Asia , Hambruna , Microbiota , Inanición/complicaciones , Adolescente , Adulto Joven , Anciano , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. METHODS: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. RESULTS: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years. CONCLUSION: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.
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Metabolic syndrome (MetS) is a complex metabolic disorder with a global prevalence of 20%-25%. Early identification and intervention would help minimize the global burden on healthcare systems. Here, we measured over 400 proteins from â¼20,000 proteomes using data-independent acquisition mass spectrometry for 7,890 serum samples from a longitudinal cohort of 3,840 participants with two follow-up time points over 10 years. We then built a machine-learning model for predicting the risk of developing MetS within 10 years. Our model, composed of 11 proteins and the age of the individuals, achieved an area under the curve of 0.774 in the validation cohort (n = 242). Using linear mixed models, we found that apolipoproteins, immune-related proteins, and coagulation-related proteins best correlated with MetS development. This population-scale proteomics study broadens our understanding of MetS and may guide the development of prevention and targeted therapies for MetS.
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Síndrome Metabólico , Humanos , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Pronóstico , Proteómica , Proteoma , Aprendizaje AutomáticoRESUMEN
While the human gut is home to a complex and diverse community of microbes, including bacteria and fungi, research on the gut microbiome has largely focused on bacteria, with relatively little attention given to the gut mycobiome. This study aims to investigate how diets with different dietary macronutrient distributions impact the gut mycobiome. We investigated gut mycobiome response to high-carbohydrate, low-fat (HC) and low-carbohydrate high-fat (LC) diet interventions based on a series of 72-day feeding-based n-of-1 clinical trials. A total of 30 participants were enrolled and underwent three sets of HC and LC dietary interventions in a randomized sequence. Each set lasted for 24 days with a 6-day washout period between dietary interventions. We collected and analyzed the fungal composition of 317 stool samples before and after each intervention period. To account for intra-individual variation across the three sets, we averaged the mycobiome data from the repeated sets for analysis. Of the 30 participants, 28 (aged 22-34 years) completed the entire intervention. Our results revealed a significant increase in gut fungal alpha diversity (p < 0.05) and significant changes in fungal composition (beta diversity, p < 0.05) after the HC dietary intervention. Specifically, we observed the enrichment of five fungal genera (Pleurotus, Kazachstania, Auricularia, Paraphaeosphaeria, Ustilaginaceae sp.; FDR < 0.052) and depletion of one fungal genus (Blumeria; FDR = 0.03) after the HC intervention. After the LC dietary intervention, one fungal genus was enriched (Ustilaginaceae sp.; FDR = 0.003), and five fungal genera were depleted (Blumeria, Agaricomycetes spp., Malassezia, Rhizopus, and Penicillium; FDR < 0.1). This study provides novel evidence on how the gut mycobiome structure and composition change in response to the HC and LC dietary interventions and reveals diet-specific changes in the fungal genera.
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Microbioma Gastrointestinal , Micobioma , Humanos , Nutrientes , Dieta con Restricción de Grasas , CarbohidratosRESUMEN
BACKGROUND: Furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a strong biomarker of fish and n-3 polyunsaturated fatty acid (PUFA) intake. The relationship of CMPF with human health has been controversial, especially for type 2 diabetes and chronic kidney disease. OBJECTIVE: We performed a prospective cohort study to examine the association of serum CMPF with incident type 2 diabetes and chronic kidney disease. METHODS: In the Guangzhou Nutrition and Health Study, during a median follow-up of 8.8 y, we used a multivariable-adjusted Poisson regression model to investigate the association of baseline serum CMPF with the incidence of type 2 diabetes (1470 participants and 170 incident cases) and chronic kidney disease (1436 participants and 112 incident cases). We also examined the association of serial measures of serum CMPF with glycemic and renal function biomarkers. Mediation analysis was also performed to examine the contribution of CMPF in the association between marine n-3 PUFAs and risk of type 2 diabetes or chronic kidney disease. RESULTS: Each standard deviation increase in baseline serum CMPF was associated with an 18% lower risk of type 2 diabetes (relative risk: 0.82, 95% confidence interval [CI]: 0.68, 0.99) but was not associated with chronic kidney disease (relative risk: 0.95; 95% CI: 0.77-1.16). Correlation analyses of CMPF with glycemic and renal function biomarkers showed similar results. Mediation analysis suggested that serum CMPF contributed to the inverse association between erythrocyte marine n-3 PUFAs and incident type 2 diabetes (proportion mediated 37%, P-mediation = 0.022). CONCLUSIONS: Our findings suggest that serum CMPF was associated with a lower risk of type 2 diabetes but not chronic kidney disease. This study also suggests that CMPF may be a functional metabolite underlying the protective relationship between marine n-3 PUFA intake and type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Ácidos Grasos Omega-3 , Enfermedades Renales , Animales , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Ácidos Grasos , Estudios de Cohortes , Riesgo , Estudios Prospectivos , Ácidos Grasos Insaturados , Biomarcadores , FuranosRESUMEN
BACKGROUND: Longitudinally conserved microbe-microbe interactions may provide insights to understand the complex dynamic system of early-life gut microbiota among preterm infants. OBJECTIVES: We aimed to profile the covarying network of gut microbiota among preterm infants and investigate its potential influence on host growth (2-5 y). METHODS: We collected time-series stool samples (n = 717 from children and n = 116 from mothers) among 51 preterm and 51 full-term infants from birth up to 5 y of age and among 53 mothers. The included infants underwent time-series measurements of early-life gut microbiota (0-5 y) and growth (2-5 y) from June 2014 to April 2017. The covarying taxa that exhibited consistent covariation from day 1 to year 5 were defined as conserved features in the development of gut microbiota. Childrens' height-for-age z score (HAZ) and weight-for-age z score were calculated according to World Health Organization Child Growth Standards. RESULTS: We observed distinct dynamic patterns of both microbial alpha and beta diversity comparing preterm infants with full-term controls during the very early stage (<3 mo). Moreover, we identified a covarying network containing 10 taxa as a conserved gut microbial feature of these preterm infants from birth to 5 y old. This covarying network was distinctive between preterm and full-term infants before 3 mo of age (P < 0.001) and tended to be similar as the infants grew up. Several covarying taxa of the network during early life (<3 mo) were associated with childhood growth (2-5 y) (eg, Clostridium_sensu_stricto_1 with HAZ, ß = -0.32, q < 0.01), and the human milk feeding duration was a main modulating factor. CONCLUSIONS: Preterm born children possess conserved and distinct covarying microbiota during very early life, which may have a profound influence on their growth later in life. This trial was registered at clinicaltrials.gov as NCT03373721.
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Microbioma Gastrointestinal , Recien Nacido Prematuro , Niño , Femenino , Humanos , Lactante , Recién Nacido , Leche Humana , Estudios ProspectivosRESUMEN
Identification of protein quantitative trait loci (pQTL) helps understand the underlying mechanisms of diseases and discover promising targets for pharmacological intervention. For most important class of drug targets, genetic evidence needs to be generalizable to diverse populations. Given that the majority of the previous studies were conducted in European ancestry populations, little is known about the protein-associated genetic variants in East Asians. Based on data-independent acquisition mass spectrometry technique, we conduct genome-wide association analyses for 304 unique proteins in 2,958 Han Chinese participants. We identify 195 genetic variant-protein associations. Colocalization and Mendelian randomization analyses highlight 60 gene-protein-phenotype associations, 45 of which (75%) have not been prioritized in Europeans previously. Further cross-ancestry analyses uncover key proteins that contributed to the differences in the obesity-induced diabetes and coronary artery disease susceptibility. These findings provide novel druggable proteins as well as a unique resource for the trans-ancestry evaluation of protein-targeted drug discovery.
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Enfermedades Cardiovasculares , Proteoma , Humanos , Proteoma/genética , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Fenotipo , Enfermedades Cardiovasculares/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido SimpleRESUMEN
Blood metabolome is commonly used in human studies to explore the associations of gut microbiota-derived metabolites with cardiometabolic diseases. Here, in a cohort of 1007 middle-aged and elderly adults with matched fecal metagenomic (149 species and 214 pathways) and paired fecal and blood targeted metabolomics data (132 metabolites), we find disparate associations with taxonomic composition and microbial pathways when using fecal or blood metabolites. For example, we observe that fecal, but not blood butyric acid significantly associates with both gut microbiota and prevalent type 2 diabetes. These findings are replicated in an independent validation cohort involving 103 adults. Our results suggest that caution should be taken when inferring microbiome-cardiometabolic disease associations from either blood or fecal metabolome data.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Adulto , Persona de Mediana Edad , Anciano , Humanos , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S , Metaboloma , Metabolómica/métodos , HecesRESUMEN
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 (ß, 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.
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Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Estudios Transversales , Estudios de Casos y Controles , Cognición , Encéfalo/diagnóstico por imagenRESUMEN
BACKGROUND: Dietary diversity is essential for human health. The gut ecosystem provides a potential link between dietary diversity, host metabolism, and health, yet this mechanism is poorly understood. OBJECTIVES: Here, we aimed to investigate the relation between dietary diversity and the gut environment as well as host metabolism from a multiomics perspective. METHODS: Two independent longitudinal Chinese cohorts (a discovery and a validation cohort) were included in the present study. Dietary diversity was evaluated with FFQs. In the discovery cohort (n = 1916), we performed shotgun metagenomic and 16S ribosomal ribonucleic acid (rRNA) sequencing to profile the gut microbiome. We used targeted metabolomics to quantify fecal and serum metabolites. The associations between dietary diversity and the microbial composition were replicated in the validation cohort (n = 1320). RESULTS: Dietary diversity was positively associated with α diversity of the gut microbiota. We identified dietary diversity-related gut environment features, including the microbial structure (ß diversity), 68 microbial genera, 18 microbial species, 8 functional pathways, and 13 fecal metabolites. We further found 332 associations of dietary diversity and related gut environment features with circulating metabolites. Both the dietary diversity and diversity-related features were inversely correlated with 4 circulating secondary bile acids. Moreover, 16 mediation associations were observed among dietary diversity, diversity-related features, and the 4 secondary bile acids. CONCLUSIONS: These results suggest that high dietary diversity is associated with the gut microbial environment. The identified key microbes and metabolites may serve as hypotheses to test for preventing metabolic diseases.
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Microbioma Gastrointestinal , Ácidos y Sales Biliares , China , Ecosistema , Heces/química , Humanos , Estudios Prospectivos , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: Many studies have investigated the effects of soy isoflavones on weight control, but few have focused on the role of equol, a gut-derived metabolite of daidzein with greater bioavailability than other soy isoflavones. OBJECTIVES: This study examined the association of equol production with obesity and explored the mediating roles of equol-related gut microbiota and microbial carnitine metabolites. METHODS: This 6.6-y prospective study included 2958 Chinese adults (2011 females and 947 males) aged 60.6 ± 6.0 y (mean ± SD) at baseline. Urinary equol and isoflavones were measured using HPLC-tandem MS. BMI, percentage fat mass (%FM), and serum triglycerides (TGs) were assessed every 3 y. Metagenomics sequencing and assessment of carnitine metabolites in feces were performed in a subsample of 897 participants. RESULTS: Urinary equol, but not daidzein and genistein, was independently and inversely associated with the obesity-related indicators of BMI, %FM, and a biomarker (TGs). Equol producers (EPs) had lower odds of adiposity conditions and a reduced risk of 6.6-y obesity progression than non-EPs among total participants. Gut microbial analyses indicated that EPs had higher microbiome species richness (P = 3.42 × 10-5) and significantly different ß-diversity of gut microbiota compared with the non-EP group (P = 0.001), with 20 of 162 species differing significantly. EPs (compared with non-EPs) had higher abundances of Alistipes senegalensis and Coprococcus catus but lower abundances of Ruminococcus gnavus (false discovery rate <0.05). Among the 7 determined fecal acylcarnitine metabolites, palmitoylcarnitine, oleylcarnitine 18:1, and stearylcarnitine were inversely associated with EPs but positively correlated with obesity conditions and progression. Path analyses indicated that the beneficial association between equol and obesity might be mediated by gut microbiota and decreased production of 3 acylcarnitines in feces. CONCLUSIONS: This study suggests a beneficial association between equol and obesity, mediated by the gut microbiome and acylcarnitines, in adults.This trial was registered at clinicaltrials.gov as NCT03179657.
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Microbioma Gastrointestinal , Isoflavonas , Adulto , Femenino , Humanos , Masculino , Adiposidad , Carnitina , Equol/orina , Isoflavonas/farmacología , Obesidad , Estudios Prospectivos , Persona de Mediana EdadRESUMEN
OBJECTIVES: The molecular landscape of non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer based on molecular characteristics is essential but poorly understood. In this pilot study we aimed to identify a multi-omics signature that can distinguish MIBC from NMIBC. Such a signature can assist in finding potential mechanistic biomarkers and druggable targets. METHODS: Patients diagnosed with NMIBC (n = 15) and MIBC (n = 11) were recruited at a tertiary-care hospital in Nanjing from 1 April 2021, and 31 July 2021. Blood, urine and stool samples per participant were collected, in which the serum metabolome, urine metabolome, gut microbiome, and serum extracellular vesicles (EV) proteome were quantified. The differences of the global profiles and individual omics measure between NMIBC vs. MIBC were assessed by permutational multivariate analysis and the Mann-Whitney test, respectively. Logistic regression analysis was used to assess the association of each identified analyte with NMIBC vs. MIBC, and the Spearman correlation was used to investigate the correlations between identified analytes, where both were adjusted for age, sex and smoking status. RESULTS: Among 3168 multi-omics measures that passed the quality control, 159 were identified to be differentiated in NMIBC vs. MIBC. Of these, 46 analytes were associated with bladder cancer progression. In addition, the global profiles showed significantly different urine metabolome (p = 0.029), gut microbiome (p = 0.036), and serum EV (extracellular vesicles) proteome (p = 0.039) but not serum metabolome (p = 0.059). We also observed 17 (35%) analytes that had been developed as drug targets. Multiple interactions were obtained between the identified analytes, whereas for the majority (61%), the number of interactions was at 11-20. Moreover, unconjugated bilirubin (p = 0.009) and white blood cell count (p = 0.006) were also shown to be different in NMIBC and MIBC, and associated with 11 identified omics analytes. CONCLUSIONS: The pilot study has shown promising to monitor the progression of bladder cancer by integrating multi-omics data and deserves further investigations.
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Neoplasias de la Vejiga Urinaria , Humanos , Proyectos Piloto , Pronóstico , Proteoma , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
BACKGROUND & AIMS: Previous studies suggest an interaction of CD36 genetic variant rs1527483 with n-3 polyunsaturated fatty acids (PUFAs) to modulate blood lipids. However, successful replication is lacking and the role of gut microbiome remains unclear. Here, we aimed to replicate these gene-diet interactions on blood lipids and investigate their possible associations with gut microbiome. METHODS: We evaluated the n-3 PUFA-rs1527483 interaction on blood lipids in two population-based cohorts (n = 4,786). We profiled fecal microbiome and short-chain fatty acids among 1,368 participants. The associations between n-3 PUFAs and bacterial alpha-diversity, taxonomies and short-chain fatty acids by rs1527483 genotypes were analyzed using regression models. RESULTS: CD36 rs1527483-GG carriers responded better to high n-3 PUFA exposure; higher blood HDL-C (beta (95% CI): 0.05 (0.01, 0.08) mmol/L) and lower TG (log-transformed, beta (95% CI): -0.08 (-0.14, -0.02)) were observed among participants whose n-3 PUFA exposure ranked in the top quartile comparing with those in the bottom quartile. We identified docosahexaenoic acid (DHA) as the driven individual n-3 PUFA biomarker, which showed interaction with rs1527483. Among the rs1527483-GG carriers, but not other genotype groups, DHA exposure was positively associated with bacterial Faith's phylogenetic diversity, Observed OTUs, Shannon's diversity index, Dorea, Coriobacteriales Incertae Sedis spp, and fecal propionic acid levels. Another independent longitudinal cohort validated the DHA-rs1527483 interaction on gut microbiome. The identified microbial features were correlated with blood lipids, and the host biosynthesis and metabolism pathways of bile acids and aromatic amino acids. CONCLUSIONS: The present study found that higher n-3 PUFAs were associated with improved blood lipids and gut microbial features only among rs1527483-GG carriers. These findings highlight a potential role of gut microbiome to link the CD36 genetic variant, n-3 PUFAs and blood lipids, revealing a new research direction to interpret the gene-diet interaction for cardiometabolic health.