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Journal of Cachexia, Sarcopenia and... Oct 2022Several studies have examined gut microbiota and sarcopenia using 16S ribosomal RNA amplicon sequencing; however, this technique may not be able to identify altered... (Observational Study)
Observational Study
BACKGROUND
Several studies have examined gut microbiota and sarcopenia using 16S ribosomal RNA amplicon sequencing; however, this technique may not be able to identify altered specific species and functional capacities of the microbes. We performed shotgun metagenomic sequencing to compare the gut microbiome composition and function between individuals with and without sarcopenia.
METHODS
Participants were from a community-based observational study conducted among the residents of rural areas in China. Appendicular skeletal muscle mass was assessed using direct segmental multi-frequency bioelectrical impedance and grip strength using a Jamar Hydraulic Hand dynamometer. Physical performance was evaluated using the Short Physical Performance Battery, 5-time chair stand test and gait speed with the 6 m walk test. Sarcopenia and its severity were diagnosed according to the Asian Working Group for Sarcopenia 2019 algorithm. The gut microbiome was profiled by shotgun metagenomic sequencing to determine the microbial composition and function. A gut microbiota-based model for classification of sarcopenia was constructed using the random forest model, and its performance was assessed using the area under receiver-operating characteristic curve (AUC).
RESULTS
The study sample included 1417 participants (women: 58.9%; mean age: 63.3 years; sarcopenia prevalence: 10.0%). β-diversity indicated by Bray-Curtis distance (genetic level: P = 0.004; taxonomic level of species: P = 0.020), but not α-diversity indicated by Shannon index (genetic level: P = 0.962; taxonomic level of species: P = 0.922), was significantly associated with prevalent sarcopenia. After adjusting for potential confounders, participants with sarcopenia had higher relative abundance of Desulfovibrio piger (P = 0.003, Q = 0.090), Clostridium symbiosum (P < 0.001, Q = 0.035), Hungatella effluvii (P = 0.003, Q = 0.090), Bacteroides fluxus (P = 0.002, Q = 0.089), Absiella innocuum (P = 0.002, Q = 0.072), Coprobacter secundus (P = 0.002, Q = 0.085) and Clostridium citroniae (P = 0.001, Q = 0.060) than those without sarcopenia. The relative abundance of six species (Desulfovibrio piger, Clostridium symbiosum, Hungatella effluvii, Bacteroides fluxus, Absiella innocuum, and Clostridium citroniae) was also positively associated with sarcopenia severity. A differential species-based model was constructed to separate participants with sarcopenia from controls. The value of the AUC was 0.852, suggesting that model has a decent discriminative performance. Desulfovibrio piger ranked the highest in this model. Functional annotation analysis revealed that the phenylalanine, tyrosine, and tryptophan biosynthesis were depleted (P = 0.006, Q = 0.071), while alpha-Linolenic acid metabolism (P = 0.008, Q = 0.094), furfural degradation (P = 0.001, Q = 0.029) and staurosporine biosynthesis (P = 0.006, Q = 0.072) were enriched in participants with sarcopenia. Desulfovibrio piger was significantly associated with staurosporine biosynthesis (P < 0.001).
CONCLUSIONS
This large population-based observational study provided empirical evidence that alterations in the gut microbiome composition and function were observed among individuals with sarcopenia.
Topics: Bacteroides; Clostridiaceae; Clostridiales; Desulfovibrio; Female; Furaldehyde; Gastrointestinal Microbiome; Humans; Middle Aged; Phenylalanine; RNA, Ribosomal, 16S; Sarcopenia; Staurosporine; Tryptophan; Tyrosine; alpha-Linolenic Acid
PubMed: 35851765
DOI: 10.1002/jcsm.13037 -
Nature Aug 2023The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease. The development of next-generation probiotics is a...
The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease. The development of next-generation probiotics is a promising strategy to modulate the gut microbiota and improve human health; however, several key candidate next-generation probiotics are strictly anaerobic and may require synergy with other bacteria for optimal growth. Faecalibacterium prausnitzii is a highly prevalent and abundant human gut bacterium associated with human health, but it has not yet been developed into probiotic formulations. Here we describe the co-isolation of F. prausnitzii and Desulfovibrio piger, a sulfate-reducing bacterium, and their cross-feeding for growth and butyrate production. To produce a next-generation probiotic formulation, we adapted F. prausnitzii to tolerate oxygen exposure, and, in proof-of-concept studies, we demonstrate that the symbiotic product is tolerated by mice and humans (ClinicalTrials.gov identifier: NCT03728868 ) and is detected in the human gut in a subset of study participants. Our study describes a technology for the production of next-generation probiotics based on the adaptation of strictly anaerobic bacteria to tolerate oxygen exposures without a reduction in potential beneficial properties. Our technology may be used for the development of other strictly anaerobic strains as next-generation probiotics.
Topics: Animals; Humans; Mice; Butyrates; Gastrointestinal Microbiome; Oxygen; Probiotics; Aerobiosis; Faecalibacterium prausnitzii; Symbiosis; Biotechnology
PubMed: 37532933
DOI: 10.1038/s41586-023-06378-w -
Gut Jan 2021Type 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota-immunological interplay is involved in the pathophysiology of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Type 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota-immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT).
DESIGN
Patients with recent-onset (<6 weeks) T1D (18-30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition.
RESULTS
Stimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal was inversely related to residual beta cell function (r=-0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics.
CONCLUSION
FMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D.
TRIAL REGISTRATION NUMBER
NTR3697.
Topics: Adolescent; Adult; C-Peptide; Diabetes Mellitus, Type 1; Duodenum; Fecal Microbiota Transplantation; Female; Gastrointestinal Microbiome; Humans; Insulin-Secreting Cells; Male; Transplantation, Autologous; Young Adult
PubMed: 33106354
DOI: 10.1136/gutjnl-2020-322630 -
Gut Microbes 2022Human longevity has a strong familial and genetic component. Dynamic characteristics of the gut microbiome during aging associated with longevity, neural, and immune...
Human longevity has a strong familial and genetic component. Dynamic characteristics of the gut microbiome during aging associated with longevity, neural, and immune function remained unknown. Here, we aim to reveal the synergistic changes in gut microbiome associated with decline in neural and immune system with aging and further obtain insights into the establishment of microbiome homeostasis that can benefit human longevity. Based on 16S rRNA and metagenomics sequencing data for 32 longevity families including three generations, centenarians, elderly, and young groups, we found centenarians showed increased diversity of gut microbiota, severely damaged connection among bacteria, depleted in microbial-associated essential amino acid function, and increased abundance of anti-inflammatory bacteria in comparison to young and elderly groups. Some potential probiotic species, such as were enriched with aging, which might possibly support health maintenance. The level of Amyloid-β (Aβ) and brain-derived neurotrophic factor (BDNF) related to neural function showed increased and decreased with aging, respectively. The elevated level of inflammatory factors was observed in centenarians compared with young and elderly groups. The enriched in centenarians might promote longevity through up-regulating anti-inflammatory factor IL-10 expression to mediate the critical balance between health and disease. Impressively, the associated analysis for gut microbiota with the level of Aβ, BDNF, and inflammatory factors suggests could be a particularly beneficial bacteria in the improvement of impaired neural and immune function. Our results provide a rationale for targeting the gut microbiome in future clinical applications of aging-related diseases and extending life span.: : 16S ribosomal RNA; : Metagenome-assembled genomes; : Amplicon sequence variants; : Deoxyribonucleic acid; : False discovery rate: : Kyoto Encyclopedia of Genes and Genomes; : Principal coordinates analysis; : Polymerase chain reaction; : Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; : Amyloid-β (Aβ); : Brain-derived neurotrophic factor.
Topics: Aged; Aged, 80 and over; Aging; Bacteria; Brain-Derived Neurotrophic Factor; Feces; Gastrointestinal Microbiome; Humans; Immunity; Longevity; Phylogeny; RNA, Ribosomal, 16S
PubMed: 35939616
DOI: 10.1080/19490976.2022.2107288 -
Gut Microbes Dec 2023Methanogens, reductive acetogens and sulfate-reducing bacteria play an important role in disposing of hydrogen in gut ecosystems. However, how they interact with each...
Methanogens, reductive acetogens and sulfate-reducing bacteria play an important role in disposing of hydrogen in gut ecosystems. However, how they interact with each other remains largely unknown. This study cocultured (reductive acetogen), (sulfate reducer) and (methanogen). Results revealed that these three species coexisted and did not compete for hydrogen in the early phase of incubations. Sulfate reduction was not affected by and . inhibited the growth of and after 10 h incubations, and the inhibition on was associated with increased sulfide concentration. Remarkably, growth lag phase was shortened by coculturing with and . Formate was rapidly used by under high acetate concentration. Overall, these findings indicated that the interactions of the hydrogenotrophic microbes are condition-dependent, suggesting their interactions may vary in gut ecosystems.
Topics: Methanobrevibacter; Ecosystem; Gastrointestinal Microbiome; Hydrogen; Sulfates
PubMed: 37753963
DOI: 10.1080/19490976.2023.2261784 -
Scientific Reports Aug 2023Animal and human feces typically include intestinal sulfate-reducing bacteria (SRB). Hydrogen sulfide and acetate are the end products of their dissimilatory sulfate...
Animal and human feces typically include intestinal sulfate-reducing bacteria (SRB). Hydrogen sulfide and acetate are the end products of their dissimilatory sulfate reduction and may create a synergistic effect. Here, we report NADH and NADPH peroxidase activities from intestinal SRB Desulfomicrobium orale and Desulfovibrio piger. We sought to compare enzymatic activities under the influence of various temperature and pH regimes, as well as to carry out kinetic analyses of enzymatic reaction rates, maximum amounts of the reaction product, reaction times, maximum rates of the enzyme reactions, and Michaelis constants in cell-free extracts of intestinal SRB, D. piger Vib-7, and D. orale Rod-9, collected from exponential and stationary growth phases. The optimal temperature (35 °C) and pH (7.0) for both enzyme's activity were determined. The difference in trends of Michaelis constants (K) during exponential and stationary phases are noticeable between D. piger Vib-7 and D. orale Rod-9; D. orale Rod-9 showed much higher K (the exception is NADH peroxidase of D. piger Vib-7: 1.42 ± 0.11 mM) during the both monitored phases. Studies of the NADH and NADPH peroxidases-as putative antioxidant defense systems of intestinal SRB and detailed data on the kinetic properties of this enzyme, as expressed by the decomposition of hydrogen peroxide-could be important for clarifying evolutionary mechanisms of antioxidant defense systems, their etiological role in the process of dissimilatory sulfate reduction, and their possible role in the development of bowel diseases.
Topics: Animals; Humans; Antioxidants; NAD; NADP; Cell Extracts; Desulfovibrio; Peroxidases; Defense Mechanisms; Sulfates
PubMed: 37626119
DOI: 10.1038/s41598-023-41185-3 -
Aging Cell Dec 2023Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a...
Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.
Topics: Humans; Aged; Gastrointestinal Microbiome; China; Metabolome; Aging; Biomarkers; Kidney
PubMed: 38015106
DOI: 10.1111/acel.14028 -
Cells Apr 2023Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota-gut-brain axis, as...
Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota-gut-brain axis, as evidenced by elevated serum IgM/IgA to lipopolysaccharides (LPS) of Gram-negative bacteria, such as and . The latter aberrations, which point to increased gut permeability (leaky gut), are linked to activated neuro-immune and oxidative pathways in MDD. To delineate the profile and composition of the gut microbiome in Thai patients with MDD, we examined fecal samples of 32 MDD patients and 37 controls using 16S rDNA sequencing, analyzed α- (Chao1 and Shannon indices) and β-diversity (Bray-Curtis dissimilarity), and conducted linear discriminant analysis (LDA) effect size (LEfSe) analysis. Neither α- nor β-diversity differed significantly between MDD and controls. , , , , and were significantly enriched in MDD, while Gracillibacteraceae family, , and , , , , and were enriched in controls. Contradictory results have been reported for all these taxa, with the exception of , which is depleted in six different MDD studies (one study showed increased abundance), many medical disorders that show comorbidities with MDD, and animal MDD models. Our results may suggest a specific profile of compositional gut dysbiosis in Thai MDD patients, with increases in some pathobionts and depletion of some beneficial microbiota. The results suggest that depletion of may be a more universal biomarker of MDD that may contribute to increased enteral LPS load, LPS translocation, and gut-brain axis abnormalities.
Topics: Humans; Depressive Disorder, Major; Gastrointestinal Microbiome; Ruminococcus; Lipopolysaccharides; Southeast Asian People; Biomarkers
PubMed: 37174640
DOI: 10.3390/cells12091240 -
Gut Microbes 2023We report the first use of constraint-based microbial community modeling on a single individual with episodic inflammation of the gastrointestinal tract, who has a well...
We report the first use of constraint-based microbial community modeling on a single individual with episodic inflammation of the gastrointestinal tract, who has a well documented set of colonic inflammatory biomarkers, as well as metagenomically-sequenced fecal time series covering seven dates over 16 months. Between the first two time steps the individual was treated with both steroids and antibiotics. Our methodology enabled us to identify numerous time-correlated microbial species and metabolites. We found that the individual's dynamical microbial ecology in the disease state led to time-varying overproduction, compared to healthy controls, of more than 24 biologically important metabolites, including methane, thiamine, formaldehyde, trimethylamine N-oxide, folic acid, serotonin, histamine, and tryptamine. The microbe-metabolite contribution analysis revealed that some species changed metabolic pathways according to the inflammation phases. At the first time point, characterized by the highest levels of serum (complex reactive protein) and fecal (calprotectin) inflammation biomarkers, they produced L-serine or formate. The production of the compounds, through a cascade effect, was mediated by the interaction with pathogenic strains and . We integrated the microbial community metabolic models of each time point with a male whole-body, organ-resolved model of human metabolism to track the metabolic consequences of dysbiosis at different body sites. The presence of in the gut microbiome influenced the sulfur metabolism with a domino effect affecting the liver. These results revealed large longitudinal variations in an individual's gut microbiome ecology and metabolite production, potentially impacting other organs in the body. Future simulations with more time points from an individual could permit us to assess how external drivers, such as diet change or medical interventions, drive microbial community dynamics.
Topics: Humans; Male; Gastrointestinal Microbiome; Microbiota; Inflammation; Liver; Anti-Bacterial Agents; Escherichia coli
PubMed: 37438876
DOI: 10.1080/19490976.2023.2226921 -
Clinical and Translational Medicine Jun 2022Due to the increasing ageing population, neurocognitive disorders (NCDs) have been a global public health issue, and its prevention and early diagnosis are crucial. Our...
BACKGROUND
Due to the increasing ageing population, neurocognitive disorders (NCDs) have been a global public health issue, and its prevention and early diagnosis are crucial. Our previous study demonstrated that there is a significant correlation between specific populations and NCDs, but the biological characteristics of the vulnerable group predispose to NCDs are unclear. The purpose of this study is to investigate the predictors for the vulnerable group by a multi-omics analysis.
METHODS
Multi-omics approaches, including metagenomics, metabolomic and proteomic, were used to detect gut microbiota, faecal metabolites and urine exosome of 8 normal controls and 13 vulnerable elders after a rigorous screening of 400 elders in Macao. The multi-omics data were analysed using R and Bioconductor. The two-sided Wilcoxon's rank-sum test, Kruskal-Wallis rank sum test and the linear discriminant analysis effective size were applied to investigate characterized features. Moreover, a 2-year follow-up was conducted to evaluate cognitive function change of the elderly.
RESULTS
Compared with the control elders, the metagenomics of gut microbiota showed that Ruminococcus gnavus, Lachnospira eligens, Escherichia coli and Desulfovibrio piger were increased significantly in the vulnerable group. Carboxylates, like alpha-ketoglutaric acid and d-saccharic acid, and levels of vitamins had obvious differences in the faecal metabolites. There was a distinct decrease in the expression of eukaryotic translation initiation factor 2 subunit 1 (eIF2α) and amine oxidase A (MAO-A) according to the proteomic results of the urine exosomes. Moreover, the compound annual growth rate of neurocognitive scores was notably decreased in vulnerable elders.
CONCLUSIONS
The multi-omics characteristics of disturbed glyoxylate and dicarboxylate metabolism (bacteria), vitamin digestion and absorption and tricarboxylic acid cycle in vulnerable elders can serve as predictors of NCDs risk among the elderly of Macao. Intervention with them may be effective therapeutic approaches for NCDs, and the underlying mechanisms merit further exploration.
Topics: Aged; Gastrointestinal Microbiome; Humans; Macau; Metagenomics; Neurocognitive Disorders; Proteomics
PubMed: 35696554
DOI: 10.1002/ctm2.909