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Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study.

ABSTRACT: It has been reported that the composition of human gut microbiota changes with age; however, few studies have used molecular techniques to investigate the long-term, sequential changes in gut microbiota composition. In this study, we investigated the sequential changes in gut microbiota composition in newborn to centenarian Japanese subjects.Fecal samples from 367 healthy Japanese subjects between the ages of 0 and 104 years were analyzed by high-throughput sequencing of amplicons derived from the V3-V4 region of the 16S rRNA gene. Analysis based on bacterial co-abundance groups (CAGs) defined by Kendall correlations between genera revealed that certain transition types of microbiota were enriched in infants, adults, elderly individuals and both infant and elderly subjects. More positive correlations between the relative abundances of genera were observed in the elderly-associated CAGs compared with the infant- and adult-associated CAGs. Hierarchical Ward's linkage clustering based on the abundance of genera indicated five clusters, with median (interquartile range) ages of 3 (0-35), 33 (24-45), 42 (32-62), 77 (36-84) and 94 (86-98) years. Subjects were predominantly clustered with their matched age; however, some of them fell into mismatched age clusters. Furthermore, clustering based on the proportion of transporters predicted by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) showed that subjects were divided into two age-related groups, the adult-enriched and infant/elderly-enriched clusters. Notably, all the drug transporters based on Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology groups were found in the infant/elderly-enriched cluster.Our results indicate some patterns and transition points in the compositional changes in gut microbiota with age. In addition, the transporter property prediction results suggest that nutrients in the gut might play an important role in changing the gut microbiota composition with age.

SUBMITTER: Odamaki T

PROVIDER: S-EPMC4879732 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study.

Odamaki Toshitaka T Kato Kumiko K Sugahara Hirosuke H Hashikura Nanami N Takahashi Sachiko S Xiao Jin-Zhong JZ Abe Fumiaki F Osawa Ro R

BMC microbiology 20160525

<h4>Background</h4>It has been reported that the composition of human gut microbiota changes with age; however, few studies have used molecular techniques to investigate the long-term, sequential changes in gut microbiota composition. In this study, we investigated the sequential changes in gut microbiota composition in newborn to centenarian Japanese subjects.<h4>Results</h4>Fecal samples from 367 healthy Japanese subjects between the ages of 0 and 104 years were analyzed by high-throughput seq ...[more]

PMID: 27220822

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Project description:Understanding the molecular mechanisms underlying the changes observed during aging is a prerequisite to design strategies to prevent age-related diseases. Aging is associated with metabolic changes, including alteration in the brain lipid metabolism. These alterations may contribute to the development of pathophysiological conditions. Modifications in the gut microbiota composition are also observed during aging. As communication axes exist between the gut microbiota and the brain and knowing that microbiota influences the host metabolism, we speculated on whether age-associated modifications in the gut microbiota could be involved in the lipid changes observed in aging brain. For that purpose, germ-free mice were colonized by the fecal microbiota of young or old donor mice. Lipid classes and fatty acid profiles were determined in the brain (cortex), plasma and liver by thin-layer chromatography on silica gel-coated quartz rods and gas chromatography. Gut colonization by microbiota of old mice resulted in a significant increase in total monounsaturated fatty acids (MUFA) and a significant decrease in the relative amounts of cholesterol and total polyunsaturated fatty acids (PUFA) in the cortex. Among the eight most represented fatty acids in the cortex, the relative abundances of five (C18:1n-9, C22:6n-3, C20:4n-6, C18:1n-7, and C20:1n-9) were significantly altered in mice inoculated with an aged microbiota. Liquid chromatography analyses revealed that the relative abundance of major species among phosphatidyl and plasmenylcholine (PC 16:0/18:1), phosphatidyl and plasmenylethanolamine (PE 18:0/22:6), lysophosphatidylethanolamine (LPE 22:6) and sphingomyelins (SM d18:1/18:0) were significantly altered in the cortex of mice colonized by the microbiota obtained from aged donors. Transplantation of microbiota from old mice also modified the lipid class and fatty acid content in the liver. Finally, we found that the expression of several genes involved in MUFA and PUFA synthesis (Scd1, Fads1, Fads2, Elovl2, and Elovl5) was dysregulated in mice inoculated with an aged microbiota. In conclusion, our data suggest that changes in gut microbiota that are associated with aging can impact brain and liver lipid metabolisms. Lipid changes induced by an aged microbiota recapitulate some features of aging, thus pointing out the potential role of microbiota alterations in the age-related degradation of the health status.

Project description:BackgroundChronic constipation is one of the most prevalent functional gastrointestinal disorders, yet its etiology is multifactorial, and the pathophysiological mechanism is still unclear. Previous studies have shown that the gut microbiota of constipated patients differs from healthy controls; however, many discrepancies exist in the findings, and no clear link has been confirmed between chronic constipation and changes in the gut microbiota. Growing evidence indicates that age, gender, and hormone levels can affect the composition of gut microbiota. The aim of this study is to examine the overall changes in gut microbiota within a specific sub-population of patients, namely, constipated women of reproductive age.MethodsWe carried out a cross-sectional study comparing the fecal microbial composition of 30 healthy women and 29 constipated women using 16S rRNA gene sequencing. Only women of reproductive age were recruited to reduce the effects of age, gender, and hormone levels on the microbiome, and to prevent conflating the impact of these factors with the effects of constipation.ResultsThere were obvious differences in the gut microbiota in constipated women of reproductive age compared with the healthy controls, manifesting mainly as a significant increase in the abundance of Bacteroides (p < 0.05) and a significant decrease in the abundance of Proteobacteria (p < 0.01). The overall composition of the gut microbiota in each group was different, which was reflected in the ratios of Firmicutes to Bacteroidetes (F/B), which was 1.52 in the constipated group vs. 2.21 in the healthy group. Additionally, there was a significant decrease in butyrate-producing bacteria, like Roseburia and Fusicatenibacter (p < 0.01).ConclusionThe overall composition of the gut microbiota changed in constipated women of reproductive age, characterized by a loss in Proteobacteria and an increase in Bacteroidetes. Furthermore, the abundance of some butyrate-producing bacteria also reduced. These changes may reflect the unique interactions between host and some bacteria, or some bacterial metabolic products, which may be important targets for future studies to explore the pathogenesis of constipation.

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Project description:IntroductionSeveral studies have reported alterations in gut microbiota composition of Alzheimer's disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and AD biomarkers using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD).Materials and methodsWe included 170 patients from the Amsterdam Dementia Cohort, comprising 33 with AD dementia (66 ± 8 years, 46%F, mini-mental state examination (MMSE) 21[19-24]), 21 with MCI (64 ± 8 years, 43%F, MMSE 27[25-29]) and 116 with SCD (62 ± 8 years, 44%F, MMSE 29[28-30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Biomarkers of AD included cerebrospinal fluid (CSF) amyloid-beta 1-42 (amyloid) and phosphorylated tau (p-tau), and MRI visual scores (medial temporal atrophy, global cortical atrophy, white matter hyperintensities). Associations between gut microbiota composition and dichotomized AD biomarkers were assessed with machine learning classification models. The two models with the highest area under the curve (AUC) were selected for logistic regression, to assess associations between the 20 best predicting microbes and the outcome measures from these machine learning models while adjusting for age, sex, BMI, diabetes, medication use, and MMSE.ResultsThe machine learning prediction for amyloid and p-tau from microbiota composition performed best with AUCs of 0.64 and 0.63. Highest ranked microbes included several short chain fatty acid (SCFA)-producing species. Higher abundance of [Clostridium] leptum and lower abundance of [Eubacterium] ventriosum group spp., Lachnospiraceae spp., Marvinbryantia spp., Monoglobus spp., [Ruminococcus] torques group spp., Roseburia hominis, and Christensenellaceae R-7 spp., was associated with higher odds of amyloid positivity. We found associations between lower abundance of Lachnospiraceae spp., Lachnoclostridium spp., Roseburia hominis and Bilophila wadsworthia and higher odds of positive p-tau status.ConclusionsGut microbiota composition was associated with amyloid and p-tau status. We extend on recent studies that observed associations between SCFA levels and AD CSF biomarkers by showing that lower abundances of SCFA-producing microbes were associated with higher odds of positive amyloid and p-tau status.

Project description:BackgroundLead (Pb) is a ubiquitous environmental contaminant with an array of detrimental health effects in children and adults, including neurological and immune dysfunction. Emerging evidence suggests that Pb exposure may alter the composition of the gut microbiota, however few studies have examined this association in human populations. The purpose of this study was to examine the association between urinary Pb concentration and the composition of the adult gut microbiota in a population-based sample of adults.MethodsData used in this study were collected as part of the Survey of the Health of Wisconsin (SHOW) and its ancillary microbiome study. The SHOW is a household-based health examination survey of Wisconsin residents, collecting a variety of survey data on health determinants and outcomes, as well as objective measurements of body habitus, and biological specimens including urine. The ancillary microbiome study added additional questions and biological specimen collection, including stool, from participants age 18+. Pb concentration was analyzed in urine samples, and gut microbiota composition was assessed using DNA sequencing of the 16S rRNA V4 region, extracted from stool samples. Data processing and statistical analyses were performed in mothur, Python, R, and SAS.ResultsOf 696 participants, urinary Pb concentration was highest in those age 70+, females, those with a high school diploma or lower, current and former smokers, and those without indoor pets. In adjusted models, increasing urinary Pb levels were associated with increases in microbial α-diversity (p = 0.071) and richness (p = 0.005). Differences in microbial β-diversity were significantly associated (p = 0.003) with differences in urinary Pb level. Presence of Proteobacteria, including members of the Burkholderiales, was significantly associated with increased urinary Pb.ConclusionThese results suggest that Pb exposure is associated with differences in the composition of the adult gut microbiota in a population-based human sample. Further investigation of this association is warranted.

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Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study.

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Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study.

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