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Microorganisms Aug 2023The role of the gut microbiota in modulating the risk of respiratory infections has garnered increasing attention. However, conventional clinical trials have faced...
The role of the gut microbiota in modulating the risk of respiratory infections has garnered increasing attention. However, conventional clinical trials have faced challenges in establishing the precise relationship between the two. In this study, we conducted a Mendelian randomization analysis with single nucleotide polymorphisms employed as instrumental variables to assess the causal links between the gut microbiota and respiratory infections. Two categories of bacteria, family and genus , were causally associated with the occurrence of upper respiratory tract infections (URTIs). Four categories of gut microbiota existed that were causally associated with lower respiratory tract infections (LRTIs), with order and genus showing a positive association and genus and genus showing a negative association. The metabolites and metabolic pathways only played a role in the development of LRTIs, with the metabolite deoxycholine acting negatively and menaquinol 8 biosynthesis acting positively. The identification of specific bacterial populations, metabolites, and pathways may provide new clues for mechanism research concerning therapeutic interventions for respiratory infections. Future research should focus on elucidating the potential mechanisms regulating the gut microbiota and developing effective strategies to reduce the incidence of respiratory infections. These findings have the potential to significantly improve global respiratory health.
PubMed: 37630668
DOI: 10.3390/microorganisms11082108 -
Frontiers in Endocrinology 2023There is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no...
OBJECTIVE
There is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no studies have explored their causal relationship.
METHODS
Instrumental variables of the gut microbiota (N = 13266) and gut microbiota-derived metabolites (N = 7824) were acquired, and a Mendelian randomization study was performed to explore their influence on NAFLD (1483 European cases and 17,781 European controls), ALD (2513 European cases and 332,951 European controls), and viral hepatitis risk (1971 European cases and 340,528 European controls). The main method for examining causality is inverse variance weighting (IVW).
RESULTS
IVW results confirmed that ( = 0.0249), ( = 0.0237), ( = 0.0245), ( = 0.0083), ( = 0.0163), and ( = 0.0472) were protective factors for NAFLD, and ( = 0.0120) was detrimental for NAFLD. The higher abundance of three genera, ( = 0.0388), ( = 0.0252), and ( = 0.0364), was correlated with a lower risk of ALD, while level was associated with a higher risk of ALD ( = 0.0371). The ( = 0.0069) and ( = 0.0195) were related to a higher risk of viral hepatitis. Besides, alanine ( = 0.0076) and phenyllactate ( = 0.0100) were found to be negatively correlated with NAFLD, while stachydrine (O = 0.0244) was found to be positively associated with NAFLD. The phenylacetate ( = 0.0353) and ursodeoxycholate ( = 0.0144) had a protective effect on ALD, while the threonate ( = 0.0370) exerted a detrimental influence on ALD. The IVW estimates of alanine ( = 0.0408) and cholate ( = 0.0293) showed their suggestive harmful effects against viral hepatitis, while threonate ( = 0.0401) displayed its suggestive protective effect against viral hepatitis.
CONCLUSION
In conclusion, our research supported causal links between the gut microbiome and its metabolites and NAFLD, ALD, and viral hepatitis.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Alanine; Clostridiales
PubMed: 37476494
DOI: 10.3389/fendo.2023.1159148 -
EBioMedicine Jul 2023Obesity is a risk factor for colorectal cancer (CRC). The role of gut microbiota in mediating the cancer-promoting effect of obesity is unknown.
BACKGROUND
Obesity is a risk factor for colorectal cancer (CRC). The role of gut microbiota in mediating the cancer-promoting effect of obesity is unknown.
METHODS
Azoxymethane (AOM)-treated, Apc and germ-free mice were gavaged with feces from obese individuals and control subjects respectively. The colonic tumor load and number were recorded at the endpoint in two carcinogenic models. The gut microbiota composition and colonic transcriptome were assessed by metagenomic sequencing and RNA sequencing, respectively. The anticancer effects of bacteria depleted in fecal samples of obese individuals were validated.
FINDINGS
Conventional AOM-treated and Apc mice receiving feces from obese individuals showed significantly increased colon tumor formation compared with those receiving feces from control subjects. AOM-treated mice receiving feces from obese individuals showed impaired intestinal barrier function and significant upregulation of pro-inflammatory cytokines and activation of oncogenic Wnt signaling pathway. Consistently, transferring feces from obese individuals to germ-free mice led to increased colonic cell proliferation, intestinal barrier function impairment, and induction of oncogenic and proinflammatory gene expression. Moreover, germ-free mice transplanted with feces from obese human donors had increased abundance of potential pathobiont Alistipes finegoldii, and reduced abundance of commensals Bacteroides vulgatus and Akkermansia muciniphila compared with those receiving feces from human donors with normal body mass index (BMI). Validation experiments showed that B. vulgatus and A. muciniphila demonstrated anti-proliferative effects in CRC, while A. finegoldii promoted CRC tumor growth.
INTERPRETATION
Our results supported the role of obesity-associated microbiota in colorectal carcinogenesis and identified putative bacterial candidates that may mediate its mechanisms. Microbiota modulation in obese individuals may provide new approaches to prevent or treat obesity-related cancers including CRC.
FUNDING
This work was funded by National Key Research and Development Program of China (2020YFA0509200/2020YFA0509203), National Natural Science Foundation of China (81922082), RGC Theme-based Research Scheme Hong Kong (T21-705/20-N), RGC Research Impact Fund Hong Kong (R4632-21F), RGC-CRF Hong Kong (C4039-19GF and C7065-18GF), RGC-GRF Hong Kong (14110819, 14111621), and NTU Start-Up Grant (021337-00001).
Topics: Humans; Mice; Animals; Gastrointestinal Microbiome; Colonic Neoplasms; Carcinogenesis; Obesity; Azoxymethane; Colorectal Neoplasms; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37343363
DOI: 10.1016/j.ebiom.2023.104670 -
Cell Host & Microbe Mar 2024Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of...
Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A. indistinctus-derived hippuric acid enhances the binding of peroxisome-proliferator-activated receptor γ (PPARγ) to the promoter of ATP-binding cassette subfamily G member 2 (ABCG2), which in turn boosts intestinal urate excretion. To facilitate this enhanced excretion, hippuric acid also promotes ABCG2 localization to the brush border membranes in a PDZ-domain-containing 1 (PDZK1)-dependent manner. These findings indicate that A. indistinctus and hippuric acid promote intestinal urate excretion and offer insights into microbiota-host crosstalk in the maintenance of uric acid homeostasis.
Topics: Humans; Hyperuricemia; Uric Acid; Intestines; ATP-Binding Cassette Transporters; Hippurates; Bacteroidetes
PubMed: 38412863
DOI: 10.1016/j.chom.2024.02.001 -
Food & Function Aug 2023Dysbiosis causes continuous progress of inflammatory bowel disease (IBD). Herein, we aim to explore whether Salidroside (Sal), which is a major glycoside extracted from...
Dysbiosis causes continuous progress of inflammatory bowel disease (IBD). Herein, we aim to explore whether Salidroside (Sal), which is a major glycoside extracted from L., could ameliorate dextran sulfate sodium (DSS)-induced colitis by modulating the microbiota. Results showed that oral treatment with 15 mg kg of Sal inhibited DSS-induced colitis in mice as evidenced by colon length, histological analysis, disease activity index (DAI) score, and the proportion and number of macrophages in the intestine. The gut microbiota of colitic mice was also partly restored by Sal. A fecal microbiota transplantation (FMT) study was designed to verify the causality. Compared with DSS-treated mice, FM from the Sal-treated donor mice significantly mitigated the symptoms of colitic mice, including reducing the DAI score, alleviating tissue damage, boosting the expression of mucin protein (mucin-2) and tight junction (TJ) proteins (occludin and zonula occludens-1 (ZO-1), and decreasing M1 macrophages in the gut. It was found that both Sal and FMT affected the structure and abundance of the gut microbiota as reflected by the decreased relative abundance of , , and the increased relative abundance of at the genus level. Moreover, the anti-inflammatory effect of Sal disappeared when the gut microbiota was depleted by antibiotics, demonstrating that Sal alleviated the intestinal inflammation in a gut microbiota-dependent manner. Thus, Sal could be a remarkable candidate as a functional food for colitis.
PubMed: 37504971
DOI: 10.1039/d3fo01929b -
Journal of Crohn's & Colitis Nov 2023Dietary patterns are important in managing ulcerative colitis [UC], given their influence on gut microbiome-host symbiosis and inflammation. We investigated whether the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
Dietary patterns are important in managing ulcerative colitis [UC], given their influence on gut microbiome-host symbiosis and inflammation. We investigated whether the Mediterranean Diet Pattern [MDP] vs the Canadian Habitual Diet Pattern [CHD] would affect disease activity, inflammation, and the gut microbiome in patients with quiescent UC.
METHODS
We performed a prospective, randomised, controlled trial in adults [65% female; median age 47 years] with quiescent UC in an outpatient setting from 2017 to 2021. Participants were randomised to an MDP [n = 15] or CHD [n = 13] for 12 weeks. Disease activity [Simple Clinical Colitis Activity Index] and faecal calprotectin [FC] were measured at baseline and week 12. Stool samples were analysed by 16S rRNA gene amplicon sequencing.
RESULTS
The diet was well tolerated by the MDP group. At week 12, 75% [9/12] of participants in the CHD had an FC >100 μg/g, vs 20% [3/15] of participants in the MDP group. The MDP group had higher levels of total faecal short chain fatty acids [SCFAs] [p = 0.01], acetic acid [p = 0.03], and butyric acid [p = 0.03] compared with the CHD. Furthermore, the MDP induced alterations in microbial species associated with a protective role in colitis [Alistipes finegoldii and Flavonifractor plautii], as well as the production of SCFAs [Ruminococcus bromii].
CONCLUSIONS
An MDP induces gut microbiome alterations associated with the maintenance of clinical remission and reduced FC in patients with quiescent UC. The data support that the MDP is a sustainable diet pattern that could be recommended as a maintenance diet and adjunctive therapy for UC patients in clinical remission. ClinicalTrials.gov no: NCT0305371.
Topics: Adult; Humans; Female; Middle Aged; Male; Colitis, Ulcerative; Diet, Mediterranean; Prospective Studies; RNA, Ribosomal, 16S; Canada; Inflammation; Feces; Butyric Acid; Leukocyte L1 Antigen Complex
PubMed: 37095601
DOI: 10.1093/ecco-jcc/jjad073 -
Kidney International Sep 2023Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and...
Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and preventing fibrosis. Here, we found that modifying gut microbiota with an antibiotic administered after severe ischemic kidney injury in mice, particularly with amoxicillin, accelerated recovery. These indices of recovery included increased glomerular filtration rate, diminution of kidney fibrosis, and reduction of kidney profibrotic gene expression. Amoxicillin was found to increase stool Alistipes, Odoribacter and Stomatobaculum species while significantly depleting Holdemanella and Anaeroplasma. Specifically, amoxicillin treatment reduced kidney CD4T cells, interleukin (IL)-17 CD4T cells, and tumor necrosis factor-α double negative T cells while it increased CD8T cells and PD1CD8T cells. Amoxicillin also increased gut lamina propria CD4T cells while decreasing CD8T and IL-17CD4T cells. Amoxicillin did not accelerate repair in germ-free or CD8-deficient mice, demonstrating microbiome and CD8T lymphocytes dependence for amoxicillin protective effects. However, amoxicillin remained effective in CD4-deficient mice. Fecal microbiota transplantation from amoxicillin-treated to germ-free mice reduced kidney fibrosis and increased Foxp3CD8T cells. Amoxicillin pre-treatment protected mice against kidney bilateral ischemia reperfusion injury but not cisplatin-induced AKI. Thus, modification of gut bacteria with amoxicillin after severe ischemic AKI is a promising novel therapeutic approach to accelerate recovery of kidney function and mitigate the progression of AKI to chronic kidney disease.
Topics: Animals; Mice; Acute Kidney Injury; Kidney; Reperfusion Injury; Ischemia; Fibrosis; Microbiota; Amoxicillin
PubMed: 37011727
DOI: 10.1016/j.kint.2023.03.024 -
Science Translational Medicine Nov 2023Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation... (Randomized Controlled Trial)
Randomized Controlled Trial
Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (, , , , species, , , and ) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible strains that replaced baseline extended-spectrum β-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.
Topics: Humans; Fecal Microbiota Transplantation; Anti-Bacterial Agents; Gastrointestinal Microbiome; Drug Resistance, Bacterial; Feces; Treatment Outcome
PubMed: 37910603
DOI: 10.1126/scitranslmed.abo2750 -
Frontiers in Public Health 2023Type 2 diabetes mellitus (T2DM) is a commonly observed metabolic anomaly globally, and as of the present time, there's no recognized solution. There is an increasing... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a commonly observed metabolic anomaly globally, and as of the present time, there's no recognized solution. There is an increasing body of evidence from numerous observational studies indicating a significant correlation between gut flora and metabolic disease progression, particularly in relation to T2DM. Despite this, the direct impact of gut microbiota on T2DM isn't fully understood yet.
METHODS
The summary statistical figures for intestinal microbiota were sourced from the MiBioGen consortium, while the summary statistical data for T2DM were gathered from the Genome-Wide Association Studies (GWAS) database. These datasets were used to execute a two-sample Mendelian randomization (MR) investigation. The Inverse Variance Weighted (IVW), Maximum Likelihood, MR-Egger, Weighted Median, and Weighted Models strategies were employed to assess the impact of gut microbiota on T2DM. Findings were primarily obtained using the IVW technique. Techniques like MR-Egger were employed to identify the occurrence of horizontal pleiotropy among instrumental variables. Meanwhile, Cochran's Q statistical measures were utilized to assess the variability or heterogeneity within these instrumental variables.
RESULTS
The outcomes from the IVW analysis demonstrated that the genus (OR = 0.998, 95% confidence interval: 0.996-1.000, and = 0.038), genus (OR = 0.998, 95% confidence interval: 0.997-0.999, = 0.033), genus (OR = 0.995, 95% confidence interval: 0.993-0.998, = 3.78 × 10), and genus (OR = 0.995, 95% confidence interval: 0.993-0.998, = 8.08 × 10) all acted as defense elements against type 2 diabetes. Family (OR = 1.003, 95% confidence interval: 1.001-1.005, = 0.012), family (OR = 1.0025, 95% confidence interval: 1.000-1.005, = 0.043), genus (OR = 1.003,95% confidence interval: 1.001-1.005, = 4.38 × 10), genus (OR = 1.001,95% confidence interval: 1.000-1.002 = 0.012) were risk factors for type 2 diabetes. False Discovery Rate correction was performed with finding that genus., genus, family and T2DM no longer displayed a significant causal association. In addition, no significant heterogeneity or horizontal pleiotropy was found for instrumental variable.
CONCLUSION
This MR study relies on genetic variation tools to confirm the causal effect of genus , genus , family , genus and genus on T2DM in the gut microbiome, providing new directions and strategies for the treatment and early screening of T2DM, which carries significant clinical relevance. To develop new biomarkers and better understand targeted prevention strategies for T2DM, further comprehensive investigations are required into the protective and detrimental mechanisms exerted by these five genera against T2DM.
Topics: Humans; Clinical Relevance; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Genome-Wide Association Study; Risk Factors; Mendelian Randomization Analysis
PubMed: 37808975
DOI: 10.3389/fpubh.2023.1255059 -
Alzheimer's & Dementia : the Journal of... Nov 2023The ketogenic diet (KD) is an intriguing therapeutic candidate for Alzheimer's disease (AD) given its protective effects against metabolic dysregulation and seizures....
INTRODUCTION
The ketogenic diet (KD) is an intriguing therapeutic candidate for Alzheimer's disease (AD) given its protective effects against metabolic dysregulation and seizures. Gut microbiota are essential for KD-mediated neuroprotection against seizures as well as modulation of bile acids, which play a major role in cholesterol metabolism. These relationships motivated our analysis of gut microbiota and metabolites related to cognitive status following a controlled KD intervention compared with a low-fat-diet intervention.
METHODS
Prediabetic adults, either with mild cognitive impairment (MCI) or cognitively normal (CN), were placed on either a low-fat American Heart Association diet or high-fat modified Mediterranean KD (MMKD) for 6 weeks; then, after a 6-week washout period, they crossed over to the alternate diet. We collected stool samples for shotgun metagenomics and untargeted metabolomics at five time points to investigate individuals' microbiome and metabolome throughout the dietary interventions.
RESULTS
Participants with MCI on the MMKD had lower levels of GABA-producing microbes Alistipes sp. CAG:514 and GABA, and higher levels of GABA-regulating microbes Akkermansia muciniphila. MCI individuals with curcumin in their diet had lower levels of bile salt hydrolase-containing microbes and an altered bile acid pool, suggesting reduced gut motility.
DISCUSSION
Our results suggest that the MMKD may benefit adults with MCI through modulation of GABA levels and gut-transit time.
Topics: United States; Humans; Adult; Alzheimer Disease; Diet, Fat-Restricted; Microbiota; Metabolome; Seizures; Ketone Bodies; gamma-Aminobutyric Acid
PubMed: 37017243
DOI: 10.1002/alz.13007