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Journal of Affective Disorders May 2023Several studies have linked gut microbiota to human brain activity. This study used Mendelian randomization (MR) to investigate the causal relationship between gut...
BACKGROUND
Several studies have linked gut microbiota to human brain activity. This study used Mendelian randomization (MR) to investigate the causal relationship between gut microbes and delirium.
METHODS
MR was used to select SNPs from large-scale GWAS summary data on 211 gut microbiota taxa and delirium. Inverse variance weighting (IVW), weighted median, and MR-Egger methods were used for statistical analyses. Outliers were assessed using the leave-one-out method. To avoid horizontal pleiotropy, we performed the MR-PRESSO and MR-Egger intercept tests. Cochran's Q and I values for IVW and MR-Egger were used to assess heterogeneity.
RESULTS
IVW suggested that genetic prediction of the family Desulfovibrionaceae (1.784 (1.267-2.512), P = 0.001), order Desulfovibrionales (1.501 (1.058-2.128), P = 0.023), and genus Candidatus Soleaferrea (1.322 (1.052-1.659), P = 0.016) increased the risk of delirium, but the family Oxalobacteraceae (0.841 (0.722-0.981), P = 0.027), and genera Holdemania (0.766 (0.620-0.946), P = 0.013), Ruminococcus gnavus (0.806 (0.661-0.982), P = 0.033), and Eggerthella (0.815 (0.667-0.997), P = 0.047) reduced the risk of delirium.
LIMITATIONS
(1) Limited sample size, (2) inability to assess gut microbiota interactions, and (3) limited to European populations.
CONCLUSION
Our results suggest that presence of the microbial family Desulfovibrionaceae, order Desulfovibrionales, and genus Candidatus Soleaferrea increased the risk of delirium, whereas the Oxalobacteraceae family, and the genera Holdemania, Ruminococcus gnavus, and Eggerthella decreased the risk of delirium. However, the potential of gut probiotic interventions in the prevention of perioperative delirium should be emphasized.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Causality; Delirium; Genome-Wide Association Study
PubMed: 36842654
DOI: 10.1016/j.jad.2023.02.078 -
Gut Microbes 2021The emerging evidence supports the use of prebiotics like herb-derived polysaccharides for treating nonalcoholic fatty liver disease (NAFLD) by modulating gut...
The emerging evidence supports the use of prebiotics like herb-derived polysaccharides for treating nonalcoholic fatty liver disease (NAFLD) by modulating gut microbiome. The present study was initiated on the microbiota-dependent anti-NAFLD effect of polysaccharides (APS) extracted from Bunge in high-fat diet (HFD)-fed mice. However, the exact mechanisms underlying the beneficial effects of APS on NAFLD formation remain poorly understood.Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS. Then, targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids (SCFAs) and bacteria that were specifically enriched by APS. Further experiment was carried out to test the capacity of SCFAs-producing of identified bacterium. Finally, the anti-NAFLD efficacy of identified bacterium was tested in HFD-fed mice.Our results first demonstrated the anti-NAFLD effect of APS in HFD-fed mice and the contribution of gut microbiota. Moreover, our results indicated that SCFAs, predominantly acetic acid were elevated in APS-supplemented mice and experiment. Metagenomics revealed that from genus was not only enriched by APS, but also a potent generator of acetic acid, which showed significant anti-NAFLD effects in HFD-fed mice. In addition, modulated the hepatic gene expression pattern of lipids metabolism, particularly suppressed hepatic fatty acid synthase (FASN) and CD36 protein expression.Our results demonstrate that APS enriched is effective on attenuating hepatic steatosis possibly through producing acetic acid, and modulation on hepatic lipids metabolism in mice. Further studies are warranted to explore the long-term impacts of on host metabolism and the underlying mechanism.
Topics: Acetic Acid; Animals; Bacteria; CD36 Antigens; Desulfovibrio vulgaris; Diet, High-Fat; Fatty Acid Synthases; Fatty Acids, Volatile; Gastrointestinal Microbiome; Humans; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Probiotics
PubMed: 34125646
DOI: 10.1080/19490976.2021.1930874 -
Science (New York, N.Y.) Jul 2019The microbiota influences obesity, yet organisms that protect from disease remain unknown. During studies interrogating host-microbiota interactions, we observed the...
The microbiota influences obesity, yet organisms that protect from disease remain unknown. During studies interrogating host-microbiota interactions, we observed the development of age-associated metabolic syndrome (MetS). Expansion of and loss of Clostridia were key features associated with obesity in this model and are present in humans with MetS. T cell-dependent events were required to prevent disease, and replacement of Clostridia rescued obesity. Inappropriate immunoglobulin A targeting of Clostridia and increased antagonized the colonization of beneficial Clostridia. Transcriptional and metabolic analysis revealed enhanced lipid absorption in the obese host. Colonization of germ-free mice with Clostridia, but not , down-regulated genes that control lipid absorption and reduced adiposity. Thus, immune control of the microbiota maintains beneficial microbial populations that constrain lipid metabolism to prevent MetS.
Topics: Animals; Antibiosis; Clostridium; Desulfovibrio; Host Microbial Interactions; Intestinal Absorption; Lipid Metabolism; Metabolic Syndrome; Mice; Mice, Mutant Strains; Microbiota; Myeloid Differentiation Factor 88; Obesity; T-Lymphocytes, Regulatory
PubMed: 31346040
DOI: 10.1126/science.aat9351 -
Cell Host & Microbe Sep 2021Many genetic and environmental factors increase susceptibility to cognitive impairment (CI), and the gut microbiome is increasingly implicated. However, the identity of...
Many genetic and environmental factors increase susceptibility to cognitive impairment (CI), and the gut microbiome is increasingly implicated. However, the identity of gut microbes associated with CI risk, their effects on CI, and their mechanisms remain unclear. Here, we show that a carbohydrate-restricted (ketogenic) diet potentiates CI induced by intermittent hypoxia in mice and alters the gut microbiota. Depleting the microbiome reduces CI, whereas transplantation of the risk-associated microbiome or monocolonization with Bilophila wadsworthia confers CI in mice fed a standard diet. B. wadsworthia and the risk-associated microbiome disrupt hippocampal synaptic plasticity, neurogenesis, and gene expression. The CI is associated with microbiome-dependent increases in intestinal interferon-gamma (IFNg)-producing Th1 cells. Inhibiting Th1 cell development abrogates the adverse effects of both B. wadsworthia and environmental risk factors on CI. Together, these findings identify select gut bacteria that contribute to environmental risk for CI in mice by promoting inflammation and hippocampal dysfunction.
Topics: Animals; Bilophila; Cognitive Dysfunction; Diet, Ketogenic; Gastrointestinal Microbiome; Hippocampus; Hypoxia, Brain; Interferon-gamma; Mice; Mice, Inbred C57BL; Mice, Knockout; Th1 Cells
PubMed: 34358434
DOI: 10.1016/j.chom.2021.07.004 -
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 -
Frontiers in Endocrinology 2022As a metabolic disease, one important feature of non-alcoholic fatty liver disease (NAFLD) is the disturbance of the intestinal flora. Spleen-strengthening and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
As a metabolic disease, one important feature of non-alcoholic fatty liver disease (NAFLD) is the disturbance of the intestinal flora. Spleen-strengthening and liver-draining formula (SLF) is a formula formed according to the theory of "One Qi Circulation" (Qing Dynasty, 1749) of Traditional Chinese Medicine (TCM), which has shown significant therapeutic effect in patients with NAFLD in a preliminary clinical observation. In this study, we aim to explore the mechanism of SLF against NAFLD, especially its effect on glucolipid metabolism, from the perspective of intestinal flora.
METHODS
A prospective, randomized, controlled clinical study was designed to observe the efficacy and safety of SLF in the treatment of NAFLD. The study participants were randomly and evenly divided into control group and treatment group (SLF group). The control group made lifestyle adjustments, while the SLF group was treated with SLF on top of the control group. Both groups were participated in the study for 12 consecutive weeks. Furthermore, the feces of the two groups were collected before and after treatment. The intestinal flora of each group and healthy control (HC) were detected utilizing 16S rRNA gene sequencing.
RESULTS
Compared with the control group, the SLF group showed significant improvements in liver function, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM), meanwhile, patients had significantly lower lipid and homeostasis model assessment of insulin resistance (HOMA-IR) with better security. Intestinal flora 16S rRNA gene sequencing results indicated reduced flora diversity and altered species abundance in patients with NAFLD. At the phylum level, levels were reduced. Although and did not differ significantly between HC and NAFLD, when grouped by alanine transaminase (ALT) and aspartate transaminase (AST) levels in NAFLD, levels were significantly higher in patients with ALT or AST abnormalities, while was significantly lower. Clinical correlation analysis showed that positively correlated with gender, age, ALT, AST, LSM, and Fibroscan-AST (FAST) score, while the opposite was true for . At the genus level, the levels of , , , , group , , , and were reduced, whereas abundance of increased. There was no statistically significant difference in and levels in the SLF group before and after treatment, but both bacteria tended to retrace. At the genus level, ( family), ( family), and ( family) were significantly higher in the SLF group after treatment, and there was also a tendency for ( family) to be back-regulated toward HC.
CONCLUSIONS
SLF can improve liver function and glucolipid metabolism in patients with NAFLD and lower down liver fat content to some extent. SLF could be carried out by regulating the disturbance of intestinal flora, especially , group, and genus.
Topics: Humans; Clostridiales; Gastrointestinal Microbiome; Non-alcoholic Fatty Liver Disease; RNA, Ribosomal, 16S; Spleen; Drugs, Chinese Herbal
PubMed: 36743913
DOI: 10.3389/fendo.2022.1107071 -
Nature Communications Mar 2021Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical...
Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4 effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8 effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia, and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.
Topics: Aged; Akkermansia; Blood Pressure; Body Mass Index; Body Weight; Desulfovibrionaceae; Diet; Fasting; Feces; Female; Gastrointestinal Microbiome; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Ruminococcus; T-Lymphocyte Subsets
PubMed: 33785752
DOI: 10.1038/s41467-021-22097-0 -
Frontiers in Microbiology 2023A growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut...
BACKGROUND
A growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut microbiota and COPD remains unclear. As a result, we used a two-sample Mendelian randomization (MR) method to investigate the connection between gut microbiota and COPD in this study.
METHODS
The largest available genome-wide association study (GWAS) of gut microbiota was obtained from the MiBioGen consortium. Summary-level dataset for COPD were obtained from the FinnGen consortium. The main analysis method for determining the causal link between gut microbiota and COPD was inverse variance weighted (IVW). Subsequently, pleiotropy and heterogeneity tests were performed to determine the reliability of the results.
RESULTS
IVW method identified 9 bacterial taxa nominally associated with the risk of COPD. Class Actinobacteria ( = 0.020), genus ( = 0.024), genus ( = 0.002) and genus ( = 0.018) were protective against COPD. In addition, order Desulfovibrionales ( = 0.011), family Desulfovibrionaceae ( = 0.039), family Peptococcaceae ( = 0.020), family Victivallaceae ( = 0.012) and genus ( = 0.017) were associated with a higher risk of COPD. No pleiotropy or heterogeneity were found.
CONCLUSION
According to the findings of this MR analysis, a causal relationship exists between certain gut microbiota and COPD. New insights into the mechanisms of COPD mediated by gut microbiota are provided.
PubMed: 37405157
DOI: 10.3389/fmicb.2023.1196751 -
Nutrients Oct 2020A high-fat diet (HFD) can easily induce obesity and change the gut microbiota and its metabolites. However, studies on the effects of high-fat diets on the host have... (Comparative Study)
Comparative Study
A high-fat diet (HFD) can easily induce obesity and change the gut microbiota and its metabolites. However, studies on the effects of high-fat diets on the host have drawn inconsistent results. In this study, the unexpected results showed that the refined HFD increased gut microbiota diversity and short-chain fatty acids (SCFAs), causing an increase in energy metabolism. Further analysis revealed these changes were caused by the different fiber content in these two diets. Male C57BL/6J mice (4-5 weeks old) were fed either HFD or refined low-fat diet (LFD) for 14 weeks. The metabolic rates, thermogenesis, gut microbiome, and intestinal SCFAs were tested. The HFD triggered obesity and disturbed glucose homeostasis. Mice fed HFD ingested more fiber than mice fed LFD ( < 0.0001), causing higher intestinal SCFA concentrations related to the increased abundances of specific bacteria in the HFD group. Also, the HFD increased metabolic heat and up-regulated thermogenesis genes uncoupling protein 1(), peroxisome proliferator-activated receptor-γ coactivator-1α () expression in the brown adipose tissue (BAT). It was revealed by 16S rRNA gene sequencing that the HFD increased gut microbial diversity, which enriched Desulfovibrionaceae, , and , meanwhile, reduced the abundance of , , , , and . The predicted metabolic pathways indicated HFD increased the gene expression of non-absorbed carbohydrate metabolism pathways, as well as the risks of colonization of intestinal pathogens and inflammation. In conclusion, the HFD was obesogenic in male C57BL/6J mice, and increased fiber intake from the HFD drove an increase in gut microbiota diversity, SCFAs, and energy expenditure. Meanwhile, the differences in specific nutrient intake can dissociate broad changes in energy expenditure, gut microbiota, and its metabolites from obesity, raising doubts in the previous studies. Therefore, it is necessary to consider whether differences in specific nutrient intake will interfere with the results of the experiments.
Topics: Animals; Bacteria; Biodiversity; Blood Glucose; Diet, Fat-Restricted; Diet, High-Fat; Dietary Carbohydrates; Dietary Fiber; Energy Metabolism; Fatty Acids, Volatile; Gastrointestinal Microbiome; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Nutrients; Obesity
PubMed: 33092019
DOI: 10.3390/nu12103197 -
Journal of Advanced Research Oct 2023The perturbations of gut microbiota could interact with excessively activated immune responses and play key roles in the etiopathogenesis of ulcerative colitis (UC)....
INTRODUCTION
The perturbations of gut microbiota could interact with excessively activated immune responses and play key roles in the etiopathogenesis of ulcerative colitis (UC). Desulfovibrio, the most predominant sulfate reducing bacteria (SRB) resided in the human gut, was observed to overgrow in patients with UC. The interactions between specific gut microbiota and drugs and their impacts on UC treatment have not been demonstrated well.
OBJECTIVES
This study aimed to elucidate whether Desulfovibrio vulgaris (D. vulgaris, DSV) and its flagellin could activate nucleotide-binding oligomerization domain-like receptors (NLR) family of apoptosis inhibitory proteins (NAIP) / NLR family caspase activation and recruitment domain-containing protein 4 (NLRC4) inflammasome and promote colitis, and further evaluate the efficacy of eugeniin targeting the interaction interface of D. vulgaris flagellin (DVF) and NAIP to attenuate UC.
METHODS
The abundance of DSV and the occurrence of macrophage pyroptosis in human UC tissues were investigated. Colitis in mice was established by dextran sulfate sodium (DSS) and gavaged with DSV or its purified flagellin. NAIP/NLRC4 inflammasome activation and macrophage pyroptosis were evaluated in vivo and in vitro. The effects of eugeniin on blocking the interaction of DVF and NAIP/NLRC4 and relieving colitis were also assessed.
RESULTS
The abundance of DSV increased in the feces of patients with UC and was found to be associated with disease activity. DSV and its flagellin facilitated DSS-induced colitis in mice. Mechanistically, RNA sequencing showed that gene expression associated with inflammasome complex and pyroptosis was upregulated after DVF treatment in macrophages. DVF was further demonstrated to induce significant macrophage pyroptosis in vitro, depending on NAIP/NLRC4 inflammasome activation. Furthermore, eugeniin was screened as an inhibitor of the interface between DVF and NAIP and successfully alleviated the proinflammatory effect of DVF in colitis.
CONCLUSION
Targeting DVF-induced NAIP/NLRC4 inflammasome activation and macrophage pyroptosis ameliorates UC. This finding is of great significance for exploring the gut microbiota-host interactions in UC development and providing new insights for precise treatment.
Topics: Humans; Mice; Animals; Inflammasomes; Flagellin; Desulfovibrio vulgaris; Colitis, Ulcerative; Macrophages; Calcium-Binding Proteins; CARD Signaling Adaptor Proteins; Neuronal Apoptosis-Inhibitory Protein
PubMed: 37586642
DOI: 10.1016/j.jare.2023.08.008