The role of gut microbiota in liver regeneration

Xu, Zhe; Jiang, Nan; Xiao, Yuanyuan; Yuan, Kefei; Wang, Zhen

doi:10.3389/fimmu.2022.1003376

Cited by 19 publications

(9 citation statements)

References 216 publications

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“…Metagenomic sequencing studies have established associations between the gut microbiome and inflammatory cytokines have been established through metagenomic sequencing studies. Gut microbes and their metabolites alter levels of various inflammatory cytokines ( 47 – 49 ). A study has shown that chronic alcohol consumption disrupts the gut microbial environment, leading to significant decreases in the levels of some of these key gut microbes (e.g., Helicobacter, a genus of Bacteroides), which in turn alters the body’s microenvironment, resulting in altered levels of inflammatory cytokines in the body, and ultimately an increased risk of infertility ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study

Zou,

Xu,

et al. 2024

Front. Endocrinol.

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IntroductionStudies have shown that the gut microbiota is associated with male infertility (MI). However, their causal relationship and potential mediators need more evidence to prove. We aimed to investigate the causal relationship between the gut microbiome and MI and the potential mediating role of inflammatory cytokines from a genetic perspective through a Mendelian randomization approach.MethodsThis study used data from genome-wide association studies of gut microbes (Mibiogen, n = 18, 340), inflammatory cytokines (NFBC1966, FYPCRS, FINRISK 1997 and 2002, n=13, 365), and male infertility (Finngen, n=120, 706) to perform two-way Mendelian randomization (MR), mediated MR, and multivariate MR(MVMR) analyses. In this study, the inverse variance weighting method was used as the primary analysis method, and other methods were used as supplementary analysis methods.ResultsIn the present study, two gut microbes and two inflammatory cytokines were found to have a potential causal relationship with MI. Of the two gut microorganisms causally associated with male infertility, Anaerotruncus increased the risk of male infertility (odds ratio = 1.81, 95% confidence interval = 1.18-2.77, P = 0.0062), and Bacteroides decreased the risk of male infertility (odds ratio = 0.57, 95% confidence interval = 0.33-0.96, P = 0.0363). In addition, of the two inflammatory cytokines identified, hepatocyte growth factor(HGF) reduced the risk of male infertility (odds ratio = 0.50, 95% confidence interval = 0.35-0.71, P = 0.0001), Monocyte chemotactic protein 3 (MCP-3) increased the risk of male infertility (odds ratio = 1.28, 95% confidence interval = 1.03-1.61, P = 0.0039). Mediated MR analysis showed that HGF mediated the causal effect of Bacteroides on MI (mediated percentage 38.9%). Multivariate MR analyses suggest that HGF may be one of the pathways through which Bacteroides affects MI, with other unexplored pathways.ConclusionThe present study suggests a causal relationship between specific gut microbiota, inflammatory cytokines, and MI. In addition, HGF may mediate the relationship between Bacteroides and MI.

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Section: Discussionmentioning

confidence: 99%

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study

Zou,

Xu,

et al. 2024

Front. Endocrinol.

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“…On the one hand, the gut microbiota plays a crucial role in influencing the occurrence and progression of metabolic liver diseases. Conversely, it impacts hepatocyte regeneration by intricately modulating key cytokines, including interleukin-6, tumor necrosis factor-α, and hepatocyte growth factor, among others, and the levels of essential metabolites in the liver’s metabolic processes, such as bile acids, lipopolysaccharide, and short-chain fatty acids ( Xu et al, 2022 ). In this experiment, we measured serum ALT and AST levels to scrutinize the impact of modeling drugs on the liver.…”

Section: Discussionmentioning

confidence: 99%

The dysfunction in intestinal microorganisms and enzyme activity as significant contributors to diarrhea with kidney-yang deficiency syndrome

Zhou,

Li,

Wang

et al. 2024

Front. Microbiol.

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ObjectTo investigate the pathogenesis of diarrhea with kidney-yang deficiency syndrome by examining characteristic changes in intestinal microorganisms, enzyme activities, oxidative stress, and metabolism indices.MethodsTwenty mice were randomly and equally divided into control group (NC) and model group (NM). Mice in NM group received adenine suspension at a dosage of 50 mg/(kg⋅day) by gavage, 0.4 mL/time, once a day for 14 days, and Folium sennae decoction at a dosage of 10 g/(kg⋅day) by gavage, 0.4 mL/time, once a day for 7 days, starting on 8th day. Mice in NC group were administered an equivalent amount of sterile water by gavage once a day for 7 days, and twice a day from the 8th day. After modeling, assessments encompassed microbial culture, organ index calculation, microbial and enzyme activity detection, malondialdehyde (MDA) content determination, superoxide dismutase (SOD) activity, blood biochemical tests, and observation of kidney tissue pathological changes.ResultsThe results showed that in NM group, a reduction in the number of Lactobacillus and Bifidobacteria was noted, accompanied by an increase in the number of bacteria and E. coli. Xylanase activity in the intestinal contents and mucosa, protease activity in the intestinal mucosa, and intestinal mucosa microbial activity were diminished. Conversely, the activities of amylase, sucrase, and lactase increased in intestinal mucosa. Additionally, there was an elevation in the level of MDA. Renal tubular dilatation and inflammatory cell infiltration were observed in the renal interstitium.ConclusionThese dysfunctions in intestinal microorganisms and enzyme activities suggest potential involvement in diarrhea with kidney-yang deficiency syndrome.

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“…SCFAs have multiple effects on T cell activation and their immune effector functions. By inhibiting histone deacetylases (HDACs), butyrate and propionate may also play a significant role in inducing the differentiation and anti-inflammatory properties of T regulatory cells (Xu et al, 2022;Blake et al, 2023;Khantakova and Sennikov, 2023;Yang et al, 2023). Moreover, polyamines could facilitate the differentiation and maturation of intestinal immune cells, whereas metabolic disorders in the intestinal microbiota led to altered arginine metabolism and decreased serum polyamine levels, thereby altering the normal intestinal immune response (Wei et al, 2020;Cheng et al, 2022).…”

Section: Gut Microbial Metabolitesmentioning

confidence: 99%

The significance of gut microbiota in the etiology of autoimmune hepatitis: a narrative review

Sun,

Zhu,

Zhu

et al. 2024

Front. Cell. Infect. Microbiol.

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Autoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver that is mediated by autoimmunity and has complex pathogenesis. Its prevalence has increased globally. Since the liver is the first organ to be exposed to harmful substances, such as gut-derived intestinal microbiota and its metabolites, gut health is closely related to liver health, and the “liver-gut axis” allows abnormalities in the gut microbiota to influence the development of liver-related diseases such as AIH. Changes in the composition of the intestinal microbiota and its resultant disruption of the intestinal barrier and microbial transport are involved in multiple ways in the disruption of immune homeostasis and inflammation, thereby influencing the development of AIH. In terms of the mechanisms involved in immune, the gut microbiota or its metabolites, which is decreased in secondary bile acids, short-chain fatty acids (SCFAs), and polyamines, and increased in lipopolysaccharide (LPS), branched-chain amino acids (BCAA), tryptophan metabolite, amino acid, and bile acid, can disrupt immune homeostasis by activating various immune cells and immune-related signaling pathways, resulting in aberrant activation of the immune system. Clarifying this mechanism has significant clinical implications for the treatment of AIH with drugs that target intestinal microbiota and related signaling pathways. Therefore, this narrative review summarizes the progress in exploring the involvement of gut microbiota in the pathogenesis of AIH, with the aim of helping to improve the precise targeting of therapeutic treatments against AIH for the benefit of clinical AIH treatment.

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The role of gut microbiota in liver regeneration

Cited by 19 publications

References 216 publications

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study

The dysfunction in intestinal microorganisms and enzyme activity as significant contributors to diarrhea with kidney-yang deficiency syndrome

The significance of gut microbiota in the etiology of autoimmune hepatitis: a narrative review

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