Casual effects of gut microbiota on risk of infections: a two-sample Mendelian randomization study

Lyu, Beibei; Ma, Jinghang; Bai, Yongyu; Feng, Zhen

doi:10.3389/fmicb.2023.1284723

Cited by 5 publications

(3 citation statements)

References 44 publications

(48 reference statements)

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“…The role of NB1n in NAFLD has not been previously reported, and to the best of our knowledge, this study is the first to identify NB1n as a harmful bacterium in NAFLD. While NB1n has been associated with infections ( Lyu et al, 2023 ; Yan et al, 2023 ) and urolithiasis ( Zhang L. et al, 2023 ), its role in the development of NAFLD remains unclear. On the other hand, the specific role of Oxalobacteraceae in NAFLD is also completely unclear.…”

Section: Discussionmentioning

confidence: 99%

Impact of gut microbiota on nonalcoholic fatty liver disease: insights from a leave-one-out cross-validation study

Pan,

Su,

Zhang

et al. 2024

Front. Microbiol.

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IntroductionEnteric dysbacteriosis is strongly associated with nonalcoholic fatty liver disease (NAFLD). However, the underlying causal relationship remains unknown. Thus, the present study aimed to investigate the relationship between gut microbiota and NAFLD using Mendelian randomization (MR) and analyze the target genes potentially regulated by specific microbiota.MethodsBidirectional two-sample MR analysis was performed using inverse variance weighted (IVW) supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Data were pooled from gut microbiota and NAFLD association studies. The least absolute shrinkage, selection operator regression, and the Support Vector Machine algorithm were used to identify genes regulated by these intestinal flora in NAFLD. The liver expression of these genes was verified in methionine choline-deficient (MCD) diet-fed mice.ResultsIVW results confirmed a causal relationship between eight specific gut microbes and NAFLD. Notably, the order Actinomycetales, NB1n, the family Actinomycetaceae, Oxalobacteraceae and the genus Ruminococcaceae UCG005 were positively correlated, whereas Lactobacillaceae, the Christensenellaceae R7 group, and Intestinibacter were negatively correlated with NAFLD onset. In NAFLD, these eight bacteria regulated four genes: colony-stimulating factor 2 receptor β, fucosyltransferase 2, 17-beta-hydroxysteroid dehydrogenase 14, and microtubule affinity regulatory kinase 3 (MAPK3). All genes, except MARK3, were differentially expressed in the liver tissues of MCD diet-fed mice.DiscussionThe abundance of eight gut microbiota species and NAFLD progression displayed a causal relationship based on the expression of the four target genes. Our findings contributed to the advancement of intestinal microecology-based diagnostic technologies and targeted therapies for NAFLD.

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Section: Discussionmentioning

confidence: 99%

Impact of gut microbiota on nonalcoholic fatty liver disease: insights from a leave-one-out cross-validation study

Pan,

Su,

Zhang

et al. 2024

Front. Microbiol.

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“…The f_Ruminococcaceae is also known to be significantly affected by chronic infections ( Martinez et al, 2022 ; Tran et al, 2023 ) and the administration of antibiotics ( Ross et al, 2016 ). Although direct evidence linking Ruminococcaceae UCG010 to UTI remains elusive, some studies have proposed that a higher abundance of this bacterium in the GM may correlate with decreased risks of type 2 diabetes ( Lyu et al, 2023 ), non-alcoholic fatty liver disease ( Tsai et al, 2020 ), and obesity ( Nseir et al, 2015 ), each being a risk factor for UTI. The mechanism involved in UTI could be that Ruminococcaceae UCG010 produces SCFAs ( Balmer et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study

He,

Han,

et al. 2024

Front. Microbiol.

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IntroductionThis study explored the causal connections between gut microbiota (GM), urinary tract infection (UTI), and potential metabolite mediators using Mendelian randomization (MR).MethodsWe utilized summary statistics from the most comprehensive and extensive genome-wide association studies (GWAS) available to date, including 196 bacterial traits for GM, 1,091 blood metabolites, 309 metabolite ratios, alongside UTI data from ukb-b-8814 and ebi-a-GCST90013890. Bidirectional MR analyses were conducted to investigate the causal links between GM and UTI. Subsequently, two MR analyses were performed to identify the potential mediating metabolites, followed by a two-step MR analysis to quantify the mediation proportion.ResultsOur findings revealed that out of the total 15 bacterial traits, significant associations with UTI risk were observed across both datasets. Particularly, taxon g_Ruminococcaceae UCG010 displayed a causal link with a diminished UTI risk in both datasets (ukb-b-8814: odds ratio [OR] = 0.9964, 95% confidence interval [CI] = 0.9930–0.9997, P = 0.036; GCST90013890: OR = 0.8252, 95% CI = 0.7217–0.9436, P = 0.005). However, no substantial changes in g_Ruminococcaceae UCG010 due to UTI were noted (ukb-b-8814: β = 0.51, P = 0.87; ebi-a-GCST90013890: β = −0.02, P = 0.77). Additionally, variations in 56 specific metabolites were induced by g_Ruminococcaceae UCG010, with N-acetylkynurenine (NAK) exhibiting a causal correlation with UTI. A negative association was found between g_Ruminococcaceae UCG010 and NAK (OR: 0.8128, 95% CI: 0.6647–0.9941, P = 0.044), while NAK was positively associated with UTI risk (OR: 1.0009; 95% CI: 1.0002–1.0016; P = 0.0173). Mediation analysis revealed that the association between g_Ruminococcaceae UCG010 and UTI was mediated by NAK with a mediation proportion of 5.07%.DiscussionThis MR study provides compelling evidence supporting the existence of causal relationships between specific GM taxa and UTI, along with potential mediating metabolites.

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“…The types Cyanobacteria Lentisphaerae, Spirochaetes and Synergistetes are present in the intestinal biotope in smaller quantities [12]. The bacterial composition of different parts of the intestine is specific [13][14][15]. The stomach, duodenum and proximal small intestine are mainly colonized by aerobic bacteria, including Streptococcus, Lactobacillus and Enterobacteriaceae, while the distal part of the small intestine and colon are dominated by anaerobes such as Bacteroides, Bifidobacterium, Prevotellaceae, Rikenellaceae, Lachnospiraceae, Ruminococcaceae and Clostridium [16].…”

Section: Introduction 1general Aspects Of Gut Microbiotamentioning

confidence: 99%

The Contribution of the Intestinal Microbiota to the Celiac Disease Pathogenesis along with the Effectiveness of Probiotic Therapy

Zolnikova,

Dzhakhaya,

Bueverova

et al. 2023

Microorganisms

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The development of many human disorders, including celiac disease (CD), is thought to be influenced by the microbiota of the gastrointestinal tract and its metabolites, according to current research. This study’s goal was to provide a concise summary of the information on the contribution of the intestinal microbiota to the CD pathogenesis, which was actively addressed while examining the reported pathogenesis of celiac disease (CD). We assumed that a change in gluten tolerance is formed under the influence of a number of different factors, including genetic predisposition and environmental factors. In related investigations, researchers have paid increasing attention to the study of disturbances in the composition of the intestinal microbiota and its functional activity in CD. A key finding of our review is that the intestinal microbiota has gluten-degrading properties, which, in turn, may have a protective effect on the development of CD. The intestinal microbiota contributes to maintaining the integrity of the intestinal barrier, preventing the formation of a “leaky” intestine. On the contrary, a change in the composition of the microbiota can act as a significant link in the pathogenesis of gluten intolerance and exacerbate the course of the disease. The possibility of modulating the composition of the microbiota by prescribing probiotic preparations is being considered. The effectiveness of the use of probiotics containing Lactobacillus and Bifidobacterium bacteria in experimental and clinical studies as a preventive and therapeutic agent has been documented.

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Casual effects of gut microbiota on risk of infections: a two-sample Mendelian randomization study

Cited by 5 publications

References 44 publications

Impact of gut microbiota on nonalcoholic fatty liver disease: insights from a leave-one-out cross-validation study

Impact of gut microbiota on nonalcoholic fatty liver disease: insights from a leave-one-out cross-validation study

Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study

The Contribution of the Intestinal Microbiota to the Celiac Disease Pathogenesis along with the Effectiveness of Probiotic Therapy

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