Nonalcoholic Fatty Liver Disease (NAFLD) as Model of Gut–Liver Axis Interaction: From Pathophysiology to Potential Target of Treatment for Personalized Therapy

Fianchi, Francesca; Liguori, Antonio; Gasbarrini, Antonio; Grieco, Antonio; Miele, Luca

doi:10.3390/ijms22126485

Cited by 48 publications

(53 citation statements)

References 188 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although recent studies showed that long-term storage at −80 • C (i.e., up to five years) has limited effects on 16S rRNA sequencing results of human fecal samples [60,61], we do not know how the sample storage may have affected our results, particularly for rare or low-abundance taxa. Finally, due to the bidirectional relation between gut microbiota and NAFLD [62], how the observed microbiota alterations may affect NAFLD development or progression is unclear and needs to be clarified in future studies.…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Associations between Gut Microbiome and Non-Alcoholic Fatty Liver Disease among Urban Chinese Adults

et al. 2021

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) has been linked to altered gut microbiome; however, evidence from large population-based studies is limited. We compared gut microbiome profiles of 188 male and 233 female NAFLD cases with 571 male and 567 female controls from two longitudinal studies of urban Chinese adults. History of NAFLD was assessed during surveys administered in 2004–2017. Microbiota were assessed using 16S rRNA sequencing of stool samples collected in 2015–2018. Associations of NAFLD with microbiome diversity and composition were evaluated by generalized linear or logistic regression models. Compared with controls, male cases had lower microbial α-diversity, higher abundance of genera Dialister and Streptococcus and Bifidobacterium species, lower abundance of genus Phascolarctobacterium, and lower prevalence of taxa including order RF39 (all p < 0.05). In contrast, female cases had higher α-diversity, higher abundance of genus Butyricimonas and a family of order Clostridiales, lower abundance of Dialister and Bifidobacterium species, and higher prevalence of RF39. Significant NAFLD–sex interactions were found for α-diversity and above taxa (all false discovery rate < 0.1). In conclusion, we observed sex-specific gut microbiome features related to history of NAFLD. Further studies are needed to validate our findings and evaluate the health effects of NAFLD-related gut microbiota.

show abstract

Section: Discussionmentioning

confidence: 99%

Sex-Specific Associations between Gut Microbiome and Non-Alcoholic Fatty Liver Disease among Urban Chinese Adults

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The establishment of intestinal dysbiosis characterized a critical event responsible for the impairment of gut-barrier function, becoming a catalyst for metabolic endotoxemia and disruption of multiple metabolic molecular pathways [43]. Over time, studies have focused on the close relationship between the intestine and the liver, introducing the concept of the gut-liver axis involved in the pathogenesis of several disturbances [44][45][46]. Through the portal circulation, intestinal blood and its contents reach the liver, resulting in the induction or progression of liver damage [47].…”

Section: Gut Microbiota and Kupffer Cells Influence On Insulin Resist...mentioning

confidence: 99%

The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications

Palma

Pronio

Romeo

et al. 2022

JCM

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) represents a predominant hepatopathy that is rapidly becoming the most common cause of hepatocellular carcinoma worldwide. The close association with metabolic syndrome’s extrahepatic components has suggested the nature of the systemic metabolic-related disorder based on the interplay between genetic, nutritional, and environmental factors, creating a complex network of yet-unclarified pathogenetic mechanisms in which the role of insulin resistance (IR) could be crucial. This review detailed the clinical and pathogenetic evidence involved in the NAFLD–IR relationship, presenting both the classic and more innovative models. In particular, we focused on the reciprocal effects of IR, oxidative stress, and systemic inflammation on insulin-sensitivity disruption in critical regions such as the hepatic and the adipose tissue, while considering the impact of genetics/epigenetics on the regulation of IR mechanisms as well as nutrients on specific insulin-related gene expression (nutrigenetics and nutrigenomics). In addition, we discussed the emerging capability of the gut microbiota to interfere with physiological signaling of the hormonal pathways responsible for maintaining metabolic homeostasis and by inducing an abnormal activation of the immune system. The translation of these novel findings into clinical practice could promote the expansion of accurate diagnostic/prognostic stratification tools and tailored pharmacological approaches.

show abstract

“…As widely reported, GM modulation represents a valid approach to manage many diseases, including NAFLD. In addition to probiotics, prebiotics, symbiotics, and the so-called fecal microbiota transplant (FMT) represent other methods used to restore dysbiosis [ 188 , 189 ].…”

Section: Other Therapeutic Optionsmentioning

confidence: 99%

Age-Related NAFLD: The Use of Probiotics as a Supportive Therapeutic Intervention

Campagnoli

Marchesi

Vairetti

et al. 2022

Cells

View full text Add to dashboard Cite

Human aging, a natural process characterized by structural and physiological changes, leads to alterations of homeostatic mechanisms, decline of biological functions, and subsequently, the organism becomes vulnerable to external stress or damage. In fact, the elderly population is prone to develop diseases due to deterioration of physiological and biological systems. With aging, the production of reactive oxygen species (ROS) increases, and this causes lipid, protein, and DNA damage, leading to cellular dysfunction and altered cellular processes. Indeed, oxidative stress plays a key role in the pathogenesis of several chronic disorders, including hepatic diseases, such as non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common liver disorder in the Western world, is characterized by intrahepatic lipid accumulation; is highly prevalent in the aging population; and is closely associated with obesity, insulin resistance, hypertension, and dyslipidemia. Among the risk factors involved in the pathogenesis of NAFLD, the dysbiotic gut microbiota plays an essential role, leading to low-grade chronic inflammation, oxidative stress, and production of various toxic metabolites. The intestinal microbiota is a dynamic ecosystem of microbes involved in the maintenance of physiological homeostasis; the alteration of its composition and function, during aging, is implicated in different liver diseases. Therefore, gut microbiota restoration might be a complementary approach for treating NAFLD. The administration of probiotics, which can relieve oxidative stress and elicit several anti-aging properties, could be a strategy to modify the composition and restore a healthy gut microbiota. Indeed, probiotics could represent a valid supplement to prevent and/or help treating some diseases, such as NAFLD, thus improving the already available pharmacological intervention. Moreover, in aging, intervention of prebiotics and fecal microbiota transplantation, as well as probiotics, will provide novel therapeutic approaches. However, the relevant research is limited, and several scientific research works need to be done in the near future to confirm their efficacy.

show abstract

Nonalcoholic Fatty Liver Disease (NAFLD) as Model of Gut–Liver Axis Interaction: From Pathophysiology to Potential Target of Treatment for Personalized Therapy

Cited by 48 publications

References 188 publications

Sex-Specific Associations between Gut Microbiome and Non-Alcoholic Fatty Liver Disease among Urban Chinese Adults

Sex-Specific Associations between Gut Microbiome and Non-Alcoholic Fatty Liver Disease among Urban Chinese Adults

The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications

Age-Related NAFLD: The Use of Probiotics as a Supportive Therapeutic Intervention

Contact Info

Product

Resources

About