Correlation of Gut Firmicutes/Bacteroidetes Ratio with Fibrosis and Steatosis in Patients with Non-alcoholic Fatty Liver Disease

Jasirwan, Chyntia Olivia Maurine; Muradi, Akhmadu; Hasan, Irsan; Simadibrata, Marcellus; Rinaldi, Ikhwan; Lesmana, Cosmas Rinaldi Adithya; Sulaiman, Andri Sanityoso; Kurniawan, Juferdy; Kalista, Kemal Fariz; Nababan, Saut Horas Hatoguan; Gani, Rino Alvani

doi:10.21203/rs.3.rs-23643/v1

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…Therefore, the F/B ratio often serves as a marker of intestinal microbiome performance (Hildebrandt et al, 2009). Clinical studies found that the F/B ratio of NAFLD patients was positively correlated to steatosis (Jasirwan et al, 2021). The F/B ratio increased in HFD-induced NAFLD mice and decreased following bilberry anthocyanin intervention (Nakano et al, 2020), supporting the trend observed in this study.…”

Section: A B Csupporting

confidence: 84%

Acupuncture improved hepatic steatosis in HFD-induced NAFLD rats by regulating intestinal microbiota

Wang

Wang²,

Liang³

et al. 2023

Front. Microbiol.

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BackgroundIntestinal dysbiosis has been increasingly implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Acupuncture has been shown to have beneficial effects on NAFLD, but the mechanism is not yet clear. This study explores the potential beneficial effects of acupuncture on intestinal microbiota in NAFLD.MethodsAn NAFLD model in Sprague Dawley rats was established using a high-fat diet (HFD) for 10 weeks. NAFLD rats were randomly divided into control, model, and acupuncture groups. Following acupuncture treatment over 6 weeks, automated biochemical analysis was used to measure serum lipid metabolism parameters, including levels of alanine transferase, aspartate transferase, alkaline phosphatase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The level of serum inflammatory factors interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) were measured by enzyme-linked immunosorbent assay. The characteristics of steatosis were evaluated using quantitative computed tomography, hematoxylin and eosin staining, and Oil Red O staining in the liver, while the intestinal microbiota was determined using 16S rRNA gene sequencing.ResultsAcupuncture decreased the systemic inflammatory response, ameliorated dyslipidemia, and improved liver function indexes in NAFLD model rats. Tomography and staining indicated that acupuncture reduced steatosis and infiltration of inflammatory cells in the liver. 16S rRNA analysis showed that acupuncture reduced the Firmicutes to Bacteroidetes (F/B) ratio, increased the abundance of microbiota, including Bacteroidales_S24-7_group, Prevotellaceae, Bacteroidaceae, Blautia, norank_f_Bacteroidales_S24-7_group, Bacteroides, and Prevotella_9, and decreased the abundance of Ruminococcaceae_UCG-014. Correlation analysis suggested a close correlation between lipid metabolism, inflammation factors, hepatic steatosis, and the changed intestinal microbiota.ConclusionAcupuncture can significantly improve lipid metabolism and the systemic inflammatory response in HFD-induced NAFLD rats, potentially by regulating intestinal microbiota composition.

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Section: A B Csupporting

confidence: 84%

Acupuncture improved hepatic steatosis in HFD-induced NAFLD rats by regulating intestinal microbiota

Wang

Wang²,

Liang³

et al. 2023

Front. Microbiol.

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“…Furthermore, Proteobacteria are closely associated with hepatic and intestinal metabolism. For example, the abundance of Proteobacteria is positively correlated with nonalcoholic fatty liver fibrosis in the normal body mass index population (Jasirwan et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota-dependent trimethylamine n-oxide pathway contributes to the bidirectional relationship between intestinal inflammation and periodontitis

Wang

Sun

Zhou

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundIntestinal inflammation and periodontitis influence the development of each other through the bidirectional relationship. As the intestinal microbiome metabolite, trimethylamine-N-oxide (TMAO) could contribute to chronic inflammation in the gut by influencing the gut microbial composition and intestinal immunity. Increased circulating TMAO levels often accompany clinical findings in patients with experimental periodontitis. However, the role of TMAO in the bidirectional relationship between intestinal inflammation and periodontitis remains unclear. Thus, we explored whether TMAO influences the periodontitis process by affecting intestinal immunity and microbial composition in this article.MethodsPeriodontitis was induced by unilateral ligation of the first molar in mice, and 3,3-dimethyl-1-butanol (DMB) was used as an inhibitor to reduce TMAO circulating. Twenty-five BALB/c mice were randomly assigned to five study sets (n = 5/group): no periodontitis with DMB (Control group), periodontitis (P) group, periodontitis with TMAO (P+TMAO) group, periodontitis with TMAO and DMB (P+TMAO+DMB) group, and periodontitis with DMB (P+DMB) group. The effect of TMAO was determined by assessing changes in intestinal histology, intestinal flora composition, periodontal tissue, and periodontal pro-inflammatory factors at ten days.ResultsThe outcomes indicated a marked improvement in the intestinal inflammation severity, and intestinal flora diversity was reduced. Firmicutes number and the ratio of Firmicutes/Bacteroidetes were improved in the P+TMAO group. In addition, the alveolar bone resorption and the degree of periodontal tissue inflammation were more severe in the P+TMAO group than in other groups. Immunohistochemistry showed higher levels of TGF-β and IL-1β expression in the periodontal tissues of P+TMAO.ConclusionsOur data suggest that TMAO could influence periodontal immunity and promote periodontal inflammation by affecting the intestinal microenvironment, revealing TMAO may affect the development of periodontitis through the bidirectional relationship of the oral-gut axis.

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“…However, some studies have shown inconsistent and even contradictory results [29]. In the NAFLD patients, there is an increase in Bacteroidetes and Proteobacteria, although some studies found a reduction or no change in Bacteroidetes and correspondingly a decrease in Firmicutes [30]. An investigation in adults with NAFLD indicated a statistically significant relationship between the presence of steatohepatitis and an expanded level of Clostridium coccoides (Firmicutes phylum) and a decreased level of Bacteroidetes, which happened after adjusting BMI and dietary fat [31].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, a study indicated that among the bacteria detected in the blood of T2DM patients, 90% of the bacterial DNA belonged to the Gram-negative Proteobacteria phylum [42]. Recently, a study indicated that Proteobacteria was the only phylum strongly correlated with liver fibrosis in patients with normal BMI [30]. Based on numerous studies, there are only four major phyla in the human intestinal microbiome that 90% of them are Gram-positive Firmicutes and Gram-negative Bacteroidetes, that Actinobacteria and Proteobacteria represent the remaining 10%.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota in nonalcoholic fatty liver diseases with and without type-2 diabetes mellitus

Leylabadlo¹,

Kafil

Farajnia

et al. 2021

European Journal of Gastroenterology &Amp; Hepatology

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Background and aims The association between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) is not very well described but gut microbiota composition is mentioned as a risk factor. The present study aimed to characterize the differences of dominant gut microbiota phyla among people with NAFLD as compared to T2DM and control groups. Patients and methods The major bacterial phylum of gut microbiota including Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and total bacteria of 15 NAFLD patients with T2DM, 15 NAFLD patients without T2DM, 15 patients with T2DM, and 20 healthy control subjects were assessed by a quantitative PCR (qPCR). Results NAFLD patients with T2DM had significantly higher BMI, triglyceride level, and total cholesterol level were compared with controls (Pv < 0.05). Bacteroidetes and Firmicutes phyla were significantly low in NAFLD patients with T2DM (Firmicutes, 2.55 ± 2.25, Pv 0/0002 and Bacteroidetes, 1.55 ± 2.29, Pv 0/0007), while the content of Proteobacteria and Actinobacteria was high in NAFLD patients with T2DM group and there were no significant differences between phyla with NAFLD patients with T2DM group (Pv > 0.05). Furthermore, Firmicutes copy number was lower in the separate groups of NAFLD and T2DM as compared to the healthy controls (Pv < 0.05). Conclusions This study performed gut microbiota for the first time among NAFLD and TDM patients separately and together. This investigation indicated that NAFLD patients with T2DM have a different gut composition in comparison to NAFLD, T2DM alone, which could be associated with disease development.

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Correlation of Gut Firmicutes/Bacteroidetes Ratio with Fibrosis and Steatosis in Patients with Non-alcoholic Fatty Liver Disease

Cited by 7 publications

References 26 publications

Acupuncture improved hepatic steatosis in HFD-induced NAFLD rats by regulating intestinal microbiota

Acupuncture improved hepatic steatosis in HFD-induced NAFLD rats by regulating intestinal microbiota

Gut microbiota-dependent trimethylamine n-oxide pathway contributes to the bidirectional relationship between intestinal inflammation and periodontitis

Gut microbiota in nonalcoholic fatty liver diseases with and without type-2 diabetes mellitus

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