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Non-alcoholic fatty liver disease and gut microbial dysbiosis- underlying mechanisms and gut microbiota mediated treatment strategies

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is by far the most prevalent form of liver disease worldwide. It’s also the leading cause of liver-related hospitalizations and deaths. Furthermore, there is a link between obesity and NAFLD risk. A projected 25% of the world’s population grieves from NAFLD, making it the most common chronic liver disorder. Several factors, such as obesity, oxidative stress, and insulin resistance, typically accompany NAFLD. Weight loss, lipid-lowering agents, thiazolidinediones, and metformin help prominently control NAFLD. Interestingly, pre-clinical studies demonstrate gut microbiota’s potential causal role in NAFLD. Increased intestinal permeability and unhindered transport of microbial metabolites into the liver are the major disruptions due to gut microbiome dysbiosis, contributing to the development of NAFLD by dysregulating the gut-liver axis. Hence, altering the pathogenic bacterial population using probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) could benefit patients with NAFLD. Therefore, it is crucial to acknowledge the importance of microbiota-mediated therapeutic approaches for NAFLD and comprehend the underlying mechanisms that establish a connection between NAFLD and gut microbiota. This review provides a comprehensive overview of the affiliation between dysbiosis of gut microbiota and the progress of NAFLD, as well as the potential benefits of prebiotic, probiotic, synbiotic supplementation, and FMT in obese individuals with NAFLD.

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Data Availability

No data were used in this review study.

Abbreviations

BA:

Bile acids

DNA:

deoxyribonucleic acid

FFA:

free fatty acid

FMT:

fecal microbiota transplantation

FXR:

Farnesoid X receptor

LPS:

lipopolysaccharides

mRNA:

Messenger ribonucleic acid

NAFLD:

Non-alcoholic fatty liver disease

NASH:

non-alcoholic steatohepatitis

NLR:

NOD-like receptor

NLRP3:

nucleotide-binding,and oligomerization domain-like receptor family pyrin domain-containing 3

SBAs:

Secondary bile acids

SCFA:

Short chain fatty acid

T2DM:

type 2 diabetes mellitus

TG:

triglycerides

TLR:

Toll-like receptor

TMAO:

Trimethylamine N-oxide

TNF-α:

tumor necrosis factor-alpha

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Acknowledgements

The authors thank the Tenth People’s Affiliated Hospital of Tongji University for providing the workplace to prepare the review.

Funding

This work was supported by the National Key R&D Program of China (No. 2018YFC1314101, 2016YFC1305600), National Natural Science Foundation of China (82170861, 81970677), Fundamental Research Funds for the Central Universities of Tongji University (22120190210), Clinical Research Plan of SHDC(SHDC2020CR1017B), and Shanghai Committee of Science and Technology, China (19DZ1910200, 18411951803, 17DZ1910603).

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  1. Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China

    Muthukumaran Jayachandran & Shen Qu

  2. Shanghai center of Thyroid diseases, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China

    Shen Qu

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  1. Muthukumaran Jayachandran
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Muthukumaran Jayachandran has conceptualized, written, proofread, and finalized the review; Qu Shen has conceptualized, proofread and approved the study.

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Correspondence to Shen Qu.

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Jayachandran, M., Qu, S. Non-alcoholic fatty liver disease and gut microbial dysbiosis- underlying mechanisms and gut microbiota mediated treatment strategies. Rev Endocr Metab Disord 24, 1189–1204 (2023). https://doi.org/10.1007/s11154-023-09843-z

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