Role of Microbiota-Derived Metabolites in Alcoholic and Non-Alcoholic Fatty Liver Diseases

Park, Ji-Won; Kim, Sung-Eun; Lee, Na Young; Kim, Jung-Hee; Jung, Jang-Han; Jang, Myoung-Kuk; Park, Sang Hoon; Lee, Myung-Seok; Kim, Dong Joon; Kim, Hyoung-Su; Suk, Ki Tae

doi:10.3390/ijms23010426

Cited by 54 publications

(39 citation statements)

References 165 publications

(166 reference statements)

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“…Gut dysbiosis is a predisposing condition to increased intestinal permeability, portal translocation of microorganisms, and microbial products forming microbial‐associated molecular patterns (MAMPs, as lipopolysaccharide, di‐ or triacylated lipopeptides, peptidoglycan, cell wall fragments, formylated peptides 6 ), including pathogen‐associated molecular patterns (PAMPs 7 ). MAMPs and PAMPs interact in the intestinal lamina propria, which is enriched in immune cells and in the liver at the level of the immune cells consisting of Kupffer cells and stellate cells.…”

Section: Introductionmentioning

confidence: 99%

The role of microbiota in nonalcoholic fatty liver disease

Ciaula

Bonfrate

Portincasa

2022

Eur J Clin Investigation

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Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide. Gut microbiota can play a role in the pathogenesis of NAFLD since dysbiosis is associated with reduced bacterial diversity, altered Firmicutes/Bacteroidetes ratio, a relative abundance of alcohol‐producing bacteria, or other specific genera. Changes can promote disrupted intestinal barrier and hyperpermeability, filtration of bacterial products, activation of the immune system, and pro‐inflammatory changes in the intestine, in the liver, and at a systemic level. Microbiota‐derived molecules can contribute to the steatogenic effects. The link between gut dysbiosis and NAFLD, however, is confused by several factors which include age, BMI, comorbidities, dietary components, and lifestyle. The role of toxic chemicals in food and water requires further studies in both gut dysbiosis and NAFLD. We can anticipate that gut microbiota manipulation will represent a potential therapeutic tool to delay or reverse the progression of NAFLD, paving the way to primary prevention measures.

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Section: Introductionmentioning

confidence: 99%

The role of microbiota in nonalcoholic fatty liver disease

Ciaula

Bonfrate

Portincasa

2022

Eur J Clin Investigation

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“…The human intestine harbors 500-1,500 different kinds of microorganisms, which encode more than three million genotypes at a ratio of 100 times the host genotypes and possess critical roles in host physiology (4). Recent indisputable evidence suggests that gut microbiota play the essential functions in the pathogenesis of NAFLD and its progression to NASH (5). Various mechanisms of association between gut dysbiosis and NASH pathology have been put forward (6).…”

Section: Introductionmentioning

confidence: 99%

Luteolin alleviates methionine–choline-deficient diet-induced non-alcoholic steatohepatitis by modulating host serum metabolome and gut microbiome

Guo

Luo

et al. 2022

Front. Nutr.

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Background and purposePrevious studies have indicated the protective effects of luteolin against non-alcoholic steatohepatitis (NASH), but the definite underlying mechanism still remains unclear. This study aimed to explore the metabolomic and metagenomic signatures of NASH with luteolin supplementation.Experimental approachMice were fed with a methionine–choline-deficient (MCD) diet containing 0.05% luteolin for 6 weeks. NASH severity was determined based on the liver histological observations, serum and hepatic biochemical measurements. Targeted metabolomics was conducted to identify differential metabolites in mice serum. 16S rRNA sequencing was conducted to assess the gut microbiota composition and function in mice colon.ResultsIn detail, luteolin treatment significantly alleviated MCD diet-induced hepatic lipid deposition, liver function damage, and oxidative stress. Targeted plasma metabolomics revealed that 5-hydroxyindole, LPE (0:0/22:5), indole 3-phosphate, and N-phenylacetylphenylalanine were remarkably elevated, and homogentisic acid, thiamine, KN-93, PC (16:1e/8, 9-EpETE), carnitine C9:1-OH, FFA (18:4) and carnitine C8:1 were significantly decreased in NASH group as compared to normal group, which could be profoundly reversed after luteolin treatment. 16S rRNA sequencing indicated that luteolin supplementation significantly increased Erysipelatoclostridium and Pseudomonas as well as decreased Faecalibaculum at genus level. Most importantly, a negative association between thiamine and Faecalibaculum was observed based on Spearman's correlation analysis, which may play an important role in the preventive effects of luteolin against NASH.ConclusionCollectively, luteolin may alleviate the NASH by modulating serum metabolome and gut microbiome, which supports its use as a dietary supplement for NASH prevention.

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“…Gut microbiota dysregulation plays a key role in the pathogenesis of liver diseases through the gut–liver axis. 51 The intestinal microbiota consists of various microorganisms that play a role in host homeostasis and produce a lot of metabolites, including peptides, SCFAs, and other metabolites. 52 Thus, we hypothesized that intestinal microbiota-derived metabolites of salecan exert a hepatoprotective effect.…”

Section: Discussionmentioning

confidence: 99%