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The American Journal of Clinical... Oct 2022The gut microbiota plays a fundamental role in human nutrition and metabolism and may have direct implications for type 2 diabetes and associated preconditions. An... (Review)
Review
The gut microbiota plays a fundamental role in human nutrition and metabolism and may have direct implications for type 2 diabetes and associated preconditions. An improved understanding of relations between human gut microbiota and glucose metabolism could lead to novel opportunities for type 2 diabetes prevention, but human observational studies reporting on such findings have not been extensively reviewed. Here, we review the literature on associations between gut microbiota and markers and stages of glucose dysregulation and insulin resistance in healthy adults and in adults with metabolic disease and risk factors. We present the current evidence for identified key bacteria and their potential roles in glucose metabolism independent of overweight, obesity, and metabolic drugs. We provide support for SCFAs mediating such effects and discuss the role of diet, as well as metabolites derived from diet and gut microbiota interactions. From 5983 initially identified PubMed records, 45 original studies were eligible and reviewed. α Diversity and 45 bacterial taxa were associated with selected outcomes. Six taxa were most frequently associated with glucose metabolism: Akkermansia muciniphila, Bifidobacterium longum, Clostridium leptum group, Faecalibacterium prausnitzii, and Faecalibacterium (inversely associated) and Dorea (directly associated). For Dorea and A. muciniphila, associations were independent of metabolic drugs and body measures. For A. muciniphila and F. prausnitzii, limited evidence supported SCFA mediation of potential effects on glucose metabolism. We conclude that observational studies applying metagenomics sequencing to identify species-level relations are warranted, as are studies accounting for confounding factors and investigating SCFA and postprandial glucose metabolism. Such advances in the field will, together with mechanistic and prospective studies and investigations into diet-gut microbiota interactions, have the potential to bring critical insight into roles of gut microbiota and microbial metabolites in human glucose metabolism and to contribute toward the development of novel prevention strategies for type 2 diabetes, including precision nutrition.
Topics: Adult; Diabetes Mellitus, Type 2; Fatty Acids, Volatile; Gastrointestinal Microbiome; Glucose; Humans; Prospective Studies; Verrucomicrobia
PubMed: 36026526
DOI: 10.1093/ajcn/nqac217 -
Diabetes Care Sep 2021This randomized controlled-feeding trial aimed to determine the impact of fried meat intake on the gut microbiota and fecal cometabolites and whether such impacts... (Randomized Controlled Trial)
Randomized Controlled Trial
The Association of Fried Meat Consumption With the Gut Microbiota and Fecal Metabolites and Its Impact on Glucose Homoeostasis, Intestinal Endotoxin Levels, and Systemic Inflammation: A Randomized Controlled-Feeding Trial.
OBJECTIVE
This randomized controlled-feeding trial aimed to determine the impact of fried meat intake on the gut microbiota and fecal cometabolites and whether such impacts influenced host glucose homoeostasis, intestinal endotoxin levels, and systemic inflammation.
RESEARCH DESIGN AND METHODS
A total of 117 overweight adults were randomized into two groups. Fifty-nine participants were provided fried meat four times per week, and 58 participants were restricted from fried meat intake, while holding food group and nutrient compositions constant, for 4 weeks. The gut microbiota was analyzed by 16S rRNA sequencing. Glucose and insulin concentrations at 0, 30, 60, and 120 min of an oral glucose tolerance test, fecal microbiota-host cometabolite levels, and intestinal endotoxin and inflammation serum biomarker levels were measured. The area under the curve (AUC) for insulin, insulinogenic index (IGI), and muscle insulin resistance index (MIRI) were calculated.
RESULTS
The participants who consumed fried meat had lower IGI values than the control subjects, but they had higher MIRI and AUC values of insulin and lipopolysaccharide (LPS), TNF-α, IL-10, and IL-1β levels ( < 0.05). Fried meat intake lowered microbial community richness and decreased and abundances while increasing , , and abundances ( FDR <0.05), provoking a significant shift in the fecal cometabolite profile, with lower 3-indolepropionic acid, valeric acid, and butyric acid concentrations and higher carnitine and methylglutaric acid concentrations ( FDR <0.05). Changes in these cometabolite levels were significantly associated with changes in IGI and MIRI values and LPS, FGF21, TNF-α, IL-1β, and IL-10 levels ( < 0.05).
CONCLUSIONS
Fried meat intake impaired glucose homoeostasis and increased intestinal endotoxin and systemic inflammation levels by influencing the gut microbiota and microbial-host cometabolites.
Topics: Adult; Endotoxins; Gastrointestinal Microbiome; Glucose; Homeostasis; Humans; Inflammation; Meat; RNA, Ribosomal, 16S
PubMed: 34253560
DOI: 10.2337/dc21-0099 -
Nutrients Dec 2022Probiotics could improve cognitive functions in patients with neurological disorders such as Alzheimer’s disease, but the effects on cognitive function in healthy... (Randomized Controlled Trial)
Randomized Controlled Trial
Probiotics could improve cognitive functions in patients with neurological disorders such as Alzheimer’s disease, but the effects on cognitive function in healthy older adults without cognitive impairment need further study. The purpose of this study was to investigate the effect of Bifidobacterium longum BB68S (BB68S) on cognitive functions among healthy older adults without cognitive impairment. A randomized, double-blind, placebo-controlled trial was conducted with 60 healthy older adults without cognitive impairment who were divided into probiotic or placebo groups and required to consume either a sachet of probiotic (BB68S, 5 × 1010 CFU/sachet) or placebo once daily for 8 weeks. The Montreal Cognitive Assessment (MoCA) was used as an inclusion screening tool to screen elderly participants with healthy cognitive function in our study, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function in subjects before and after intervention as an assessment tool. BB68S significantly improved subjects’ cognitive functions (total RBANS score increased by 18.89 points after intervention, p < 0.0001), especially immediate memory, visuospatial/constructional, attention, and delayed memory domains. BB68S intervention increased the relative abundances of beneficial bacteria Lachnospira, Bifidobacterium, Dorea, and Cellulosilyticum, while decreasing those of bacteria related to cognition impairment, such as Collinsella, Parabacteroides, Tyzzerella, Bilophila, unclassified_c_Negativicutes, Epulopiscium, Porphyromonas, and Granulicatella. In conclusion, BB68S could improve cognitive functions in healthy elderly adults without cognitive impairment, along with having beneficial regulatory effects on their gut microbiota. This study supports probiotics as a strategy to promote healthy aging and advances cognitive aging research.
Topics: Humans; Aged; Bifidobacterium longum; Probiotics; Cognition; Bifidobacterium; Cognitive Dysfunction; Double-Blind Method
PubMed: 36615708
DOI: 10.3390/nu15010051 -
Psychiatry Research Jan 2023This 3-month randomized psychoeducation-controlled trial (RCT) of exercise was undertaken in young adolescents with subthreshold depression to examine the impact on gut... (Randomized Controlled Trial)
Randomized Controlled Trial
This 3-month randomized psychoeducation-controlled trial (RCT) of exercise was undertaken in young adolescents with subthreshold depression to examine the impact on gut microbiota. Participants (aged 12-14 years) were randomly assigned to an exercise or a psychoeducation-controlled group. The exercise intervention arm took moderate-intensity exercise, comprised of 30 min of running per day, 4 days a week for 3 months. Psychoeducation intervention consisted of 6 sessions of group activity including gaming, reading, and singing. The gut microbiota was assessed by metagenomic sequencing. After 3-month moderate-intensity exercise, the intervention group increased the relative abundance of Coprococcus, Blautia, Dorea, Tyzzerella at the genus level, as well as Tyzzerella nexilis, Ruminococcus obeum at species level when compared to the psychoeducation-controlled group. Moreover, EggNOG analyses showed that the defense and signal transduction mechanism were highly enriched after the active intervention, and changes were correlated with improvements in depressive symptoms measured by Chinese Patient Depression Questionnaire 9. The KEGG pathway of neurodegenerative diseases was depleted in the microbiome in young adolescents with subthreshold depression after exercise intervention. This 3-month RCT suggests that at both the genus and species levels, aerobic group exercise intervention improved in depressive symptoms and revealed changes in gut microbiota suggesting beneficial effects.
Topics: Humans; Adolescent; Depression; Gastrointestinal Microbiome; Exercise
PubMed: 36565548
DOI: 10.1016/j.psychres.2022.115005 -
Frontiers in Microbiology 2023Increasing evidence from observational studies and clinical experimentation has indicated a link between the gut microbiotas (GMs) and polycystic ovary syndrome (PCOS),...
BACKGROUND
Increasing evidence from observational studies and clinical experimentation has indicated a link between the gut microbiotas (GMs) and polycystic ovary syndrome (PCOS), however, the causality and direction of causality between gut microbiome and PCOS remains to be established.
METHODS
We conducted a comprehensive search of four databases-PubMed, Cochrane Library, Web of Science, and Embase up until June 1, 2023, and subjected the results to a meta-analysis. In this study, a bidirectional two-sample Mendelian randomization (MR) analysis was employed to investigate the impact of gut microbiota on polycystic ovary syndrome (PCOS). The genome-wide association study (GWAS) data for PCOS comprised 113,238 samples, while the GWAS data for gut microbiota were derived from the MiBioGen consortium, encompassing a total sample size of 18,340 individuals. As the largest dataset of its kind, this study represents the most comprehensive genome-wide meta-analysis concerning gut microbiota composition to date. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables at various taxonomic levels, including Phylum, Class, Order, Family, and Genus. The causal associations between exposures and outcomes were assessed using four established MR methods. To correct for multiple testing, the false discovery rate (FDR) method was applied. The reliability and potential biases of the results were evaluated through sensitivity analysis and F-statistics.
RESULTS
The meta-analysis incorporated a total of 20 studies that met the criteria, revealing a close association between PCOS and specific gut microbiota species. As per the results from our MR analysis, we identified six causal associations between the gut microbiome and polycystic ovary syndrome (PCOS). At the genus level, (OR = 1.369, = 0.040), (OR = 1.548, = 0.027), and (OR = 1.488, = 0.028) were identified as risk factors for PCOS. Conversely, (OR = 0.723, = 0.040), (OR = 0.580, = 0.032), and (OR = 0.732, = 0.030) were found to be protective factors against PCOS. Furthermore, the MR-PRESSO global test and MR-Egger regression indicated that our study results were not affected by horizontal pleiotropy ( > 0.05). Finally, the leave-one-out analysis corroborated the robustness of the MR findings.
CONCLUSION
Both our meta-analysis and MR study indicates that there is a causal relationship between the gut microbiome and PCOS, which may contribute to providing novel insights for the development of new preventive and therapeutic strategies for PCOS.
PubMed: 37555058
DOI: 10.3389/fmicb.2023.1203902 -
Nature Communications Nov 2023The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly...
The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts' prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.
Topics: Humans; Gastrointestinal Microbiome; Immune Checkpoint Inhibitors; Microbiota; Metagenome; Bacteria; Neoplasms
PubMed: 37973916
DOI: 10.1038/s41467-023-42997-7 -
Frontiers in Cellular and Infection... 2023Insomnia is the second most common mental health issue, also is a social and financial burden. Insomnia affects the balance between sleep, the immune system, and the...
INTRODUCTION
Insomnia is the second most common mental health issue, also is a social and financial burden. Insomnia affects the balance between sleep, the immune system, and the central nervous system, which may raise the risk of different systemic disorders. The gut microbiota, referred to as the "second genome," has the ability to control host homeostasis. It has been discovered that disruption of the gut-brain axis is linked to insomnia.
METHODS
In this study, we conducted MR analysis between large-scale GWAS data of GMs and insomnia to uncover potential associations.
RESULTS
Ten GM taxa were detected to have causal associations with insomnia. Among them, class , genus , genus , genus , genus , and order were linked to a higher risk of insomnia. In reverse MR analysis, we discovered a causal link between insomnia and six other GM taxa.
CONCLUSION
It suggested that the relationship between insomnia and intestinal flora was convoluted. Our findings may offer beneficial biomarkers for disease development and prospective candidate treatment targets for insomnia.
Topics: Humans; Gastrointestinal Microbiome; Sleep Initiation and Maintenance Disorders; Mendelian Randomization Analysis; Central Nervous System; Clostridiaceae; Genome-Wide Association Study
PubMed: 38089822
DOI: 10.3389/fcimb.2023.1296417 -
Frontiers in Cellular and Infection... 2023Recent studies have suggested a relationship between gut microbiota and non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the...
BACKGROUND
Recent studies have suggested a relationship between gut microbiota and non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the nature and direction of this potential causal relationship are still unclear. This study used two-sample Mendelian randomization (MR) to clarify the potential causal links.
METHODS
Summary-level Genome-Wide Association Studies (GWAS) statistical data for gut microbiota and NAFLD/NASH were obtained from MiBioGen and FinnGen respectively. The MR analyses were performed mainly using the inverse-variance weighted (IVW) method, with sensitivity analyses conducted to verify the robustness. Additionally, reverse MR analyses were performed to examine any potential reverse causal associations.
RESULTS
Our analysis, primarily based on the IVW method, strongly supports the existence of causal relationships between four microbial taxa and NAFLD, and four taxa with NASH. Specifically, associations were observed between Enterobacteriales ( =0.04), ( =0.04), ( =0.02), and ( =0.04) and increased risk of NAFLD. ( =0.03) and ( =0.04) could increase the risks of NASH while ( =0.04) and (=0.005) could decrease them. We also identified that NAFLD was found to potentially cause an increased abundance in ( =0.007) and ( =0.002). However, we found no evidence of reverse causation in the microbial taxa associations with NASH.
CONCLUSION
This study identified several specific gut microbiota that are causally related to NAFLD and NASH. Observations herein may provide promising theoretical groundwork for potential prevention and treatment strategies for NAFLD and its progression to NASH in future.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Clostridiaceae; Clostridiales
PubMed: 38106475
DOI: 10.3389/fcimb.2023.1294826 -
Scientific Reports Jun 2023Metabolic associated fatty liver disease (MAFLD) is rising in incidence and is an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). Alterations...
Metabolic associated fatty liver disease (MAFLD) is rising in incidence and is an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). Alterations in the gut microbiota have been shown to correlate with the development and progression of MAFLD. However, little is known regarding differences in the gut microbiomes of MAFLD patients and healthy cohorts, and subgroups at the abnormal activity of hepatic enzymes in China. In this study, we enrolled 81 MAFLD patients and 25 healthy volunteers. The fecal microbiota was assessed using 16S rRNA gene sequencing and metagenomic sequencing. The results suggested that Ruminococcus obeum and Alistipes were most enriched in healthy individuals when compared with MAFLD patients. Microbe-set Enrichment Analysis (MSEA) results showed Dorea, Lactobacillus and Megasphaera are enriched in MAFLD group. We also found that Alistipes has negatively related to serum glucose (GLU), gamma-glutamyl transferase (GGT), and alanine aminotransferase (ALT). Moreover, the abundance of Dorea was found to be significantly overrepresented in the MAFLD patients and the degree of enrichment increased with the increasing abnormal liver enzyme. An increase in Dorea, combined with decreases in Alistipes appears to be characteristic of MAFLD patients. Further study of microbiota may provide a novel insight into the pathogenesis of MAFLD as well as a novel treatment strategy.
Topics: Humans; Gastrointestinal Microbiome; Carcinoma, Hepatocellular; RNA, Ribosomal, 16S; Liver Neoplasms; Microbiota; Non-alcoholic Fatty Liver Disease; Bacteroidetes; Clostridiaceae
PubMed: 37340081
DOI: 10.1038/s41598-023-37163-4 -
Cell Reports May 2023Understanding the axis of the human microbiome and physiological homeostasis is an essential task in managing deep-space-travel-associated health risks. The NASA-led...
Understanding the axis of the human microbiome and physiological homeostasis is an essential task in managing deep-space-travel-associated health risks. The NASA-led Rodent Research 5 mission enabled an ancillary investigation of the gut microbiome, varying exposure to microgravity (flight) relative to ground controls in the context of previously shown bone mineral density (BMD) loss that was observed in these flight groups. We demonstrate elevated abundance of Lactobacillus murinus and Dorea sp. during microgravity exposure relative to ground control through whole-genome sequencing and 16S rRNA analyses. Specific functionally assigned gene clusters of L. murinus and Dorea sp. capable of producing metabolites, lactic acid, leucine/isoleucine, and glutathione are enriched. These metabolites are elevated in the microgravity-exposed host serum as shown by liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomic analysis. Along with BMD loss, ELISA reveals increases in osteocalcin and reductions in tartrate-resistant acid phosphatase 5b signifying additional loss of bone homeostasis in flight.
Topics: Humans; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Chromatography, Liquid; Travel; Tandem Mass Spectrometry; Space Flight
PubMed: 37080202
DOI: 10.1016/j.celrep.2023.112299