**6. Conclusions**

Intestinal dysbiosis can trigger gut inflammation and increase the permeability of the intestinal epithelial barrier, exposing the gut-liver axis to GM-derived mediators of dysbiosis, such as bacterial components or metabolites, which may induce hepatotoxicity, inflammation, and consequently NAFLD progression. Gut-derived mediators of dysbiosis contribute to NAFLD progression by activating the immune system, inducing oxidative stress, enhancing inflammation, and finally promoting fibrogenesis.

Despite the evident association between GM dysbiosis, obesity, and NAFLD derived from several experimental studies, few studies have been conducted in patients with NAFLD to explore the role of GM-derived mediators of dysbiosis in the occurrence and progression of the disease. Additionally, few studies have focused on gut-derived mediators of dysbiosis as noninvasive markers of disease progression. The study of these mediators may provide an opportunity to develop a specific diagnostic and prognostic biomarker for NAFLD and NASH. In this sense, we propose the metabolomic study of these mediators and other metabolites involved to achieve a metabolomic profile that could be used as biomarkers for evaluating the status of NAFLD. On the other hand, some previous evidence has focused on GM modulation using probiotics, prebiotics, and antibiotics as therapeutic strategies to prevent or treat NAFLD and NASH, which is more uncertain and requires future research. In this sense, it remains important to promote study of GM targeting to find an effective treatment for NAFLD and overall for NASH.

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*Intestinal Dysbiosis and Non-Alcoholic Fatty Liver Disease*

The authors declare no conflict of interest.

NAFLD non-alcoholic fatty liver disease NASH non-alcoholic steatohepatitis

GM gut microbiota

BAs bile acids

EtOH ethanol

T2DM type 2 diabetes mellitus IR insulin resistance MS metabolic syndrome LPS lipopolysaccharides SCFAs short-chain fatty acids

TMAO trimethylamine-N-oxide

NAFL non-alcoholic fatty liver

AST aspartate aminotransferase ALT alanine aminotransferase

VLDL very-low density lipoprotein GPR G-protein coupled receptors TNF-α tumor necrosis factor alpha

SIBO small intestinal bacterial overgrowth syndrome

SREBP-1c sterol-regulatory element-binding protein-1c

PPARα proliferator-activated receptor alpha

PAMPs pathogen-associated molecular patterns

SS simple steatosis

TLRs toll-like receptors

IL interleukin

CA cholic acid

NL normal liver GCA glycolic acid

LPB LPS-binding protein NF-κB necrosis factor-kappa beta

FXR farnesoid X receptor

GLP-1 glucagon-like peptide-1 AMPK AMP-activated protein kinase

CDCA chenodeoxycholic acid DCA deoxycholic acid LCA lithocholic acid NRs nuclear receptors

SHP small heterodimer partner

This study was supported by the *Fondo de Investigación Sanitaria and Fondo Europeo de Desarrollo Regional* (FEDER, grant number PI16/00498, to Teresa

Auguet), by funds from the *Agència de Gestió d'Ajuts Universitaris de Recerca* (AGAUR 2009 SGR 959 to Cristóbal Richart) and the *Grup de Recerca en Medicina Aplicada URV* (2016PFR-URV-B2-72 to Cristóbal Richart), and by the *Fundación Biociencia*.

*DOI: http://dx.doi.org/10.5772/intechopen.92972*

**Acknowledgements**

**Conflict of interest**

**Abbreviations**
