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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 -
Scientific Reports Jun 2022There is growing interest in the role of gut microbiome in colorectal cancer (CRC), ranging from screening to disease recurrence. Our study aims to identify microbial...
There is growing interest in the role of gut microbiome in colorectal cancer (CRC), ranging from screening to disease recurrence. Our study aims to identify microbial markers characteristic of CRC and to examine if changes in bacteriome persist after surgery. Forty-nine fecal samples from 25 non-cancer (NC) individuals and 12 CRC patients, before and 6-months after surgery, were collected for analysis by bacterial 16S rRNA gene sequencing. Bacterial richness and diversity were reduced, while pro-carcinogenic bacteria such as Bacteroides fragilis and Odoribacter splanchnicus were increased in CRC patients compared to NC group. These differences were no longer observed after surgery. Comparison between pre-op and post-op CRC showed increased abundance of probiotic bacteria after surgery. Concomitantly, bacteria associated with CRC progression were observed to have increased after surgery, implying persistent dysbiosis. In addition, functional pathway predictions based on the bacterial 16S rRNA gene data showed that various pathways were differentially enriched in CRC compared to NC. Microbiome signatures characteristic of CRC comprise altered bacterial composition. Elements of these dysbiotic signatures persists even after surgery, suggesting possible field-change in remnant non-diseased colon. Future studies should involve a larger sample size with microbiome data collected at multiple time points after surgery to examine if these dysbiotic patterns truly persist and also correlate with disease outcomes.
Topics: Bacteria; Colorectal Neoplasms; Dysbiosis; Humans; Neoplasm Recurrence, Local; Pilot Projects; RNA, Ribosomal, 16S
PubMed: 35701595
DOI: 10.1038/s41598-022-14203-z -
Microbiology Spectrum Feb 2022Prior study has demonstrated that gut microbiota at the genus level is significantly altered in patients with growth hormone (GH)-secreting pituitary adenoma (GHPA)....
Prior study has demonstrated that gut microbiota at the genus level is significantly altered in patients with growth hormone (GH)-secreting pituitary adenoma (GHPA). Yet, no studies exist describing the state of gut microbiota at species level in GHPA. We performed a study using 16S rRNA amplicon sequencing in a cohort of patients with GH-secreting pituitary adenoma (GHPA, = 28) and healthy controls ( = 67). Among them, 9 patients and 10 healthy controls were randomly chosen and enrolled in metagenomics shotgun sequencing, generating 280,426,512 reads after aligning to NCBI GenBank DataBase to acquire taxa information at the species level. Weighted UniFrac analysis revealed that microbial diversity was notably decreased in patients with GHPA, consistent with a previous study. With 16S rRNA sequencing, after correction for false-discovery rate (FDR), rank-sum test at the genus level revealed that the relative abundance of and was remarkably increased in patients and and genera predominated in the controls, augmented by additional LEfSe (linear discriminant analysis effect size) analysis. As for further comparison at the species level with metagenomics sequencing, rank-sum test together with LEfSe analysis confirmed the enrichment of Alistipes shahii and Odoribacter splanchnicus in the patient group. Notably, LEfSe analysis with metagenomics also demonstrated that sp. and sp. , derived from , were both significantly enriched in patients. Functional analysis showed that amino acid metabolism pathway was remarkably enriched in GHPA, while carbohydrate metabolism pathway was notably enriched in controls. Further, significant positive correlations were observed between and baseline insulin-like growth factor 1 (IGF-1), indicating that may be strongly associated with GH/IGF-1 axis in GHPA. Our data extend our insight into the GHPA microbiome, which may shed further light on GHPA pathogenesis and facilitate the exploration of novel therapeutic targets based on microbiota manipulation. Dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extraintestinal diseases. Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of GH and IGF-1, causing increased morbidity and mortality. Researches have reported that the GH/IGF-1 axis exerts its own influence on the intestinal microflora. Here, the results showed that compared with healthy controls, GHPA patients not only decreased the alpha diversity of the intestinal flora but also significantly changed their beta diversity. Further, metagenomics shotgun sequencing in the present study exhibited that sp. and sp. were enriched in patients. Also, we were pleasantly surprised to find that the genus was strongly positively correlated with baseline IGF-1 levels. Collectively, our work provides the first glimpse of the dysbiosis of the gut microbiota at species level, providing a better understanding of the pathophysiological process of GHPA.
Topics: Adult; Bacteria; Case-Control Studies; DNA, Bacterial; Dysbiosis; Feces; Female; Gastrointestinal Microbiome; Growth Hormone; Growth Hormone-Secreting Pituitary Adenoma; Humans; Insulin-Like Growth Factor I; Male; Metagenomics; Middle Aged; Phylogeny; RNA, Ribosomal, 16S
PubMed: 35019688
DOI: 10.1128/spectrum.00425-21 -
Frontiers in Medicine 2021To investigate the correlation between the structure and function alterations of gut microbiota and biochemical indicators in males with hyperuricemia (HUA) and high...
To investigate the correlation between the structure and function alterations of gut microbiota and biochemical indicators in males with hyperuricemia (HUA) and high levels of liver enzymes, in order to provide new evidences and therapeutic targets for the clinical diagnosis and treatment of HUA. A total of 69 patients with HUA (HUA group) and 118 healthy controls were enrolled in this study. Their age, height, waist circumference, weight, and pressure were measured. The clinical parameters such as fasting plasma glucose (FBG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum uric acid (SUA), serum creatinine (Scr), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), white blood cell (WBC), platelet (PLT), and absolute value of neutrophils (NEUT) were examined. We used whole-genome shotgun sequencing technology and HUMAnN2 MetaCyc pathway database to detect the composition and pathways of the gut microbiota. The main statistical methods were student's test, chi-square tests, and Wilcoxon rank sum test. The correlations among bacterial diversity, microbial pathways, and biochemical indicators were evaluated by the R function "cor.test" with spearman method. The gut bacterial diversity in HUA group reduced significantly and the community of the microbiota was of significant difference between the two groups. The pathways that can produce 5-aminoimidazole ribonucleotide (PWY-6122, PWY-6277, and PWY-6121), aromatic amino acids, and chorismate (COMPLETE-ARO-PWY, ARO-PWY, and PWY-6163) were enriched in the HUA group; while the pathways that can produce short-chain fatty acids (SCFAs, such as CENTFERM-PWY and PWY-6590) and the gut microbiotas that can produce SCFAs () and equol () were enriched in healthy controls. The structure and function of the gut microbiota in males with HUA and high levels of liver enzymes have altered apparently. In-depth study of related mechanisms may provide new ideas for the treatment of HUA.
PubMed: 34869502
DOI: 10.3389/fmed.2021.779994 -
Frontiers in Microbiology 2021The gut microbiota (GM) has been shown to be closely associated with the development of colorectal cancer (CRC). However, the involvement of GM is CRC has mainly been...
The gut microbiota (GM) has been shown to be closely associated with the development of colorectal cancer (CRC). However, the involvement of GM is CRC has mainly been demonstrated by metagenomic profiling studies showing the compositional difference between the GM of healthy individuals and that of CRC patients and not by directly studying isolated gut microbes. Thus, to discover novel gut microbes involved in CRC, we isolated the GM from the feces of healthy individuals and evaluated its anti-CRC activity and . After GM isolation, cell-free supernatants (CFSs) were prepared from the isolated gut microorganisms to efficiently screen a large amount of the GM for anti-proliferative ability . Our results showed that the CFSs of 21 GM isolates had anti-proliferative activity against human colon cancer HCT 116 cells. Of these 21 GM isolates, GM07 was chosen for additional study because it had the highest anti-cancer activity against mouse colon cancer CT 26 cells and was further evaluated in a CT 26 allograft mouse model . GM07 was identified as through phylogenetic analysis based on 16S rRNA gene sequencing. Further investigation determined that the CFS of (OsCFS) induced anti-proliferative activity apoptosis, but not cell cycle arrest. Moreover, GC/MS analysis suggested that the putative active molecule in OsCFS is malic acid. Finally, in the CRC mouse model, peri-tumoral injection of OsCFS significantly decreased CRC formation, compared to the control group. Altogether, these findings will provide valuable information for the discovery of potential probiotic candidates that inhibit CRC.
PubMed: 34867852
DOI: 10.3389/fmicb.2021.736343 -
The ISME Journal Apr 2022Irritable bowel syndrome (IBS) is one of the functional gastrointestinal disorders characterized by chronic and/or recurrent symptoms of abdominal pain and irregular...
Irritable bowel syndrome (IBS) is one of the functional gastrointestinal disorders characterized by chronic and/or recurrent symptoms of abdominal pain and irregular defecation. Changed gut microbiota has been proposed to mediate IBS; however, contradictory results exist, and IBS-specific microbiota, metabolites, and their interactions remain poorly understood. To address this issue, we performed metabolomic and metagenomic profiling of stool and serum samples based on discovery (n = 330) and validation (n = 101) cohorts. Fecal metagenomic data showed moderate dysbiosis compared with other diseases, in contrast, serum metabolites showed significant differences with greater power to distinguish IBS patients from healthy controls. Specifically, 726 differentially abundant serum metabolites were identified, including a cluster of fatty acyl-CoAs enriched in IBS. We further identified 522 robust associations between differentially abundant gut bacteria and fecal metabolites, of which three species including Odoribacter splanchnicus, Escherichia coli, and Ruminococcus gnavus were strongly associated with the low abundance of dihydropteroic acid. Moreover, dysregulated tryptophan/serotonin metabolism was found to be correlated with the severity of IBS depression in both fecal and serum metabolomes, characterized by a shift in tryptophan metabolism towards kynurenine production. Collectively, our study revealed serum/fecal metabolome alterations and their relationship with gut microbiome, highlighted the massive alterations of serum metabolites, which empower to recognize IBS patients, suggested potential roles of metabolic dysregulation in IBS pathogenesis, and offered new clues to understand IBS depression comorbidity. Our study provided a valuable resource for future studies, and would facilitate potential clinical applications of IBS featured microbiota and/or metabolites.
Topics: Comorbidity; Depression; Feces; Humans; Irritable Bowel Syndrome; Metabolome; Microbiota; Tryptophan
PubMed: 34750528
DOI: 10.1038/s41396-021-01123-5 -
Microbes and Infection Mar 2022Gut microbiota is believed to play a crucial role in obesity. However, the consistent findings among published studies regarding microbiome-obesity interaction are...
Gut microbiota is believed to play a crucial role in obesity. However, the consistent findings among published studies regarding microbiome-obesity interaction are relatively rare, and one of the underlying causes could be the limited sample size of cohort studies. In order to identify gut microbiota changes between normal-weight individuals and obese individuals, fecal samples along with phenotype information from 2262 Chinese individuals were collected and analyzed. Compared with normal-weight individuals, the obese individuals exhibit lower diversity of species and higher diversity of metabolic pathways. In addition, various machine learning models were employed to quantify the relationship between obesity status and Body mass index (BMI) values, of which support vector machine model achieves best performance with 0.716 classification accuracy and 0.485 R score. In addition to two well-established obesity-associated species, three species that have potential to be obesity-related biomarkers, including Bacteroides caccae, Odoribacter splanchnicus and Roseburia hominis were identified. Further analyses of functional pathways also reveal some enriched pathways in obese individuals. Collectively, our data demonstrates tight relationship between obesity and gut microbiota in a large-scale Chinese population. These findings may provide potential targets for the prevention and treatment of obesity.
Topics: Body Mass Index; Feces; Gastrointestinal Microbiome; Humans; Machine Learning; Obesity
PubMed: 34678464
DOI: 10.1016/j.micinf.2021.104892 -
Gastroenterology Jan 2022Fecal microbiota transplantation (FMT) is an emerging treatment modality for ulcerative colitis (UC). Several randomized controlled trials have shown efficacy for FMT in...
BACKGROUND & AIMS
Fecal microbiota transplantation (FMT) is an emerging treatment modality for ulcerative colitis (UC). Several randomized controlled trials have shown efficacy for FMT in the treatment of UC, but a better understanding of the transferable microbiota and their immune impact is needed to develop more efficient microbiome-based therapies for UC.
METHODS
Metagenomic analysis and strain tracking was performed on 60 donor and recipient samples receiving FMT for active UC. Sorting and sequencing of immunoglobulin (Ig) A-coated microbiota (called IgA-seq) was used to define immune-reactive microbiota. Colonization of germ-free or genetically engineered mice with patient-derived strains was performed to determine the mechanism of microbial impact on intestinal immunity.
RESULTS
Metagenomic analysis defined a core set of donor-derived transferable bacterial strains in UC subjects achieving clinical response, which predicted response in an independent trial of FMT for UC. IgA-seq of FMT recipient samples and gnotobiotic mice colonized with donor microbiota identified Odoribacter splanchnicus as a transferable strain shaping mucosal immunity, which correlated with clinical response and the induction of mucosal regulatory T cells. Colonization of mice with O splanchnicus led to an increase in Foxp3/RORγt regulatory T cells, induction of interleukin (IL) 10, and production of short chain fatty acids, all of which were required for O splanchnicus to limit colitis in mouse models.
CONCLUSIONS
This work provides the first evidence of transferable, donor-derived strains that correlate with clinical response to FMT in UC and reveals O splanchnicus as a key component promoting both metabolic and immune cell protection from colitis. These mechanistic features will help enable strategies to enhance the efficacy of microbial therapy for UC. Clinicaltrials.gov ID NCT02516384.
Topics: Animals; Bacteroidetes; Clinical Trials as Topic; Colitis; Colitis, Ulcerative; Colon; Disease Models, Animal; Fecal Microbiota Transplantation; Forkhead Transcription Factors; Gastrointestinal Microbiome; Germ-Free Life; Humans; Immunity, Mucosal; Immunoglobulin A; Intestinal Mucosa; Intraepithelial Lymphocytes; Metagenome; Metagenomics; Mice, Inbred C57BL; Mice, Knockout; Nuclear Receptor Subfamily 1, Group F, Member 3; T-Lymphocytes, Regulatory; Treatment Outcome; Mice
PubMed: 34606847
DOI: 10.1053/j.gastro.2021.09.061 -
MicrobiologyOpen Jun 2021Obesity has become a major public health problem in recent decades. More effective interventions may result from a better understanding of microbiota alterations caused...
Obesity has become a major public health problem in recent decades. More effective interventions may result from a better understanding of microbiota alterations caused by weight loss and diet. Our objectives were (a) to calculate the fiber composition of a specially designed low-calorie weight loss diet (WLD), and (b) to evaluate changes in the composition of gut microbiota and improvements in health characteristics during WLD. A total of 19 overweight/obese participants were assigned to 20%-40% reduced calories low-carbohydrate high-fat diet for four weeks. Protein and fat content in the composed diet was 1.5 times higher compared to that in the average diet of the normal weight reference group, while carbohydrate content was 2 times lower. Food consumption data were obtained from the assigned meals. Microbial composition was analyzed before and after WLD intervention from two sequential samples by 16S rRNA gene sequencing. During WLD, body mass index (BMI) was reduced on average 2.5 ± 0.6 kg/m and stool frequency was normalized. The assigned diet induced significant changes in fecal microbiota. The abundance of bile-resistant bacteria (Alistipes, Odoribacter splanchnicus), Ruminococcus bicirculans, Butyricimonas, and Enterobacteriaceae increased. Importantly, abundance of bacteria often associated with inflammation such as Collinsella and Dorea decreased in parallel with a decrease in BMI. Also, we observed a reduction in bifidobacteria, which can be attributed to the relatively low consumption of grains. In conclusion, weight loss results in significant alteration of the microbial community structure.
Topics: Adult; Bacteria; Body Mass Index; DNA, Bacterial; Diet, Carbohydrate-Restricted; Diet, High-Fat; Feces; Female; Gastrointestinal Microbiome; Humans; Male; Obesity; Overweight; Phylogeny; RNA, Ribosomal, 16S; Weight Loss
PubMed: 34180599
DOI: 10.1002/mbo3.1194 -
Cell Host & Microbe Jun 2021In this issue of Cell Host & Microbe,Xing et al. (2021) show that gut microbiota confer resistance to colitis and colon cancer by stimulating IL-6 and IL-1β production...
In this issue of Cell Host & Microbe,Xing et al. (2021) show that gut microbiota confer resistance to colitis and colon cancer by stimulating IL-6 and IL-1β production and Th17 cell expansion. Their findings reveal that even a single bacterial strain, Odoribacter splanchnicus, can confer protective immunity against cancer.
Topics: Bacteroidetes; Colitis; Humans; Immunity, Innate; Microbiota; Neoplasms; Th17 Cells
PubMed: 34111391
DOI: 10.1016/j.chom.2021.05.005