Restoration of a healthy intestinal microbiota normalizes portal hypertension in a rat model of nonalcoholic steatohepatitis

García‐Lezana, Teresa; Raurell, Imma; Bravo, Miren; Torres-Arauz, M.; Salcedo, María Teresa; Santiago, Alba; Schoenenberger, A; Manichanh, Chaysavanh; Genescà, Joan; Martell, Marı́a; Augustín, Salvador

doi:10.1002/hep.29646

Cited by 101 publications

(104 citation statements)

References 29 publications

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“…Metagenomic analysis found reduced abundance of Bacteroides and increased abundance of Firmicutes in the HFGFD group. Importantly, transplantation of gut microbiota from control to HFGFD animals restored insulin sensitivity, normalized endothelial dysfunction and reduced intrahepatic vascular resistance even as HFGFD feeding continued, although NAFLD histological scores remained unchanged . These findings indicate that the link between gut microbiota and PHT involves nonstructural (dynamic) components since the impact was independent of the presence and degree of liver fibrosis.…”

Section: Host‐microbiota Interactions and The Beginnings Of Portal Hymentioning

confidence: 79%

“…All animals receiving HFGFD developed steatohepatitis (steatosis, ballooning and lobular inflammation) with mild or absent fibrosis. Importantly, HFGFD was associated with significantly higher portal pressure compared to the control group and amounts of phosphorylated Akt and eNOS in the liver were reduced, consistent with insulin‐dependent endothelial dysfunction . Notably, faecal transplant derived from the HFGFD group was not sufficient to induce PHT in control animals.…”

Section: Host‐microbiota Interactions and The Beginnings Of Portal Hymentioning

confidence: 87%

“…In a recent study, rats were fed with high‐fat, high glucose/fructose diet (HFGFD) or control diet for 8 weeks and received autologous or heterologous faecal microbiota transplantation from similarly treated rats to ascertain the impact of gut microbiota on metabolic, histological and hemodynamic features of experimental NAFLD . All animals receiving HFGFD developed steatohepatitis (steatosis, ballooning and lobular inflammation) with mild or absent fibrosis.…”

Section: Host‐microbiota Interactions and The Beginnings Of Portal Hymentioning

confidence: 99%

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Potential mechanisms linking gut microbiota and portal hypertension

Baffy

2018

Liver International

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Gut microbiota is the largest collection of commensal micro‐organisms in the human body, engaged in reciprocal cellular and molecular interactions with the liver. This mutually beneficial relationship may break down and result in dysbiosis, associated with disease phenotypes. Altered composition and function of gut microbiota has been implicated in the pathobiology of nonalcoholic fatty liver disease (NAFLD), a prevalent condition linked to obesity, insulin resistance and endothelial dysfunction. NAFLD may progress to cirrhosis and portal hypertension, which is the result of increased intrahepatic vascular resistance and altered splanchnic circulation. Gut microbiota may contribute to rising portal pressure from the earliest stages of NAFLD, although the significance of these changes remains unclear. NAFLD has been linked to lower microbial diversity and weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defence and inflammation. Moreover, disrupted host‐microbial metabolic interplay alters bile acid signalling and the release of vasoregulatory gasotransmitters. These perturbations become prominent in cirrhosis, increasing the risk of clinically significant portal hypertension and leading to bacterial translocation, sepsis and acute‐on‐chronic liver failure. Better understanding of the gut‐liver axis and identification of novel microbial molecular targets may yield specific strategies in the prevention and management of portal hypertension.

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Section: Host‐microbiota Interactions and The Beginnings Of Portal Hymentioning

confidence: 79%

Section: Host‐microbiota Interactions and The Beginnings Of Portal Hymentioning

confidence: 87%

Section: Host‐microbiota Interactions and The Beginnings Of Portal Hymentioning

confidence: 99%

See 1 more Smart Citation

Potential mechanisms linking gut microbiota and portal hypertension

Baffy

2018

Liver International

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“…García-Lezana et al (2018) showed that FMT restored a healthy intestinal microbiota and normalized portal hypertension in a rat model of NASH. Zhou et al (2017a) reported that FMT attenuated high-fat diet-induced NASH in mice via beneficial regulation of gut microbiota.…”

Section: The Microbiome As a Potential Therapeutic Target In Nafld Anmentioning

confidence: 97%

The role of the microbiome in NAFLD and NASH

et al. 2018

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Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of cardiometabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. It is rapidly becoming the most prevalent liver disease worldwide. A sizable minority of NAFLD patients develop nonalcoholic steatohepatitis (NASH), which is characterized by inflammatory changes that can lead to progressive liver damage, cirrhosis, and hepatocellular carcinoma. Recent studies have shown that in addition to genetic predisposition and diet, the gut microbiota affects hepatic carbohydrate and lipid metabolism as well as influences the balance between pro‐inflammatory and anti‐inflammatory effectors in the liver, thereby impacting NAFLD and its progression to NASH. In this review, we will explore the impact of gut microbiota and microbiota‐derived compounds on the development and progression of NAFLD and NASH, and the unexplored factors related to potential microbiome contributions to this common liver disease.

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“…2 More recent studies suggest that the manipulation of the gut microbiome, either with antibiotics or FMT, also suppresses liver tumorigenesis and reduces portal hypertension in murine models. 3, 4 …”

mentioning

confidence: 99%

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

Sharpton

Ajmera

Loomba

2019

Clinical Gastroenterology and Hepatology

136

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The gut microbiome, a diverse microbial community in the gastrointestinal tract, plays a pivotal role in the maintenance of health. The gut microbiome metabolizes dietary and host-derived molecules to produce bioactive metabolites, which have a wide array of effects on host metabolism and immunity. 'Dysbiosis' of the gut microbiome, commonly considered as perturbation of microbiome diversity and composition, has been associated with intestinal and extra-intestinal diseases, including nonalcoholic fatty liver disease (NAFLD). A number of endogenous and exogenous factors, such as nutritional intake and xenobiotic exposure, can alter the gut microbiome. We will review the evolving methods for studying the gut microbiome and how these profiling techniques have been utilized to further our understanding of the gut microbial community composition and functional potential in the clinical spectrum of NAFLD. We will highlight microbiome-host interactions that may contribute to the pathogenesis of NAFLD, with a primary focus on mechanisms related to the metabolic output of the gut microbiome. Finally, we will discuss potential therapeutic implications of the gut microbiome in NAFLD.

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Restoration of a healthy intestinal microbiota normalizes portal hypertension in a rat model of nonalcoholic steatohepatitis

Abstract: The IM exerts a direct influence in the development of PH in rats with diet-induced NASH and dysbiosis; PH, insulin resistance, and endothelial dysfunction revert when a healthy IM is restored. (Hepatology 2018;67:1485-1498).

Cited by 101 publications

References 29 publications

Potential mechanisms linking gut microbiota and portal hypertension

Potential mechanisms linking gut microbiota and portal hypertension

The role of the microbiome in NAFLD and NASH

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

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