The Intestinal Microbiome, Plasma Metabolome, and Liver Transcriptome: A Conspiracy Driving Hepatic Steatosis

Mehal, Wajahat Z.; Loomba, Rohit

doi:10.1002/hep.30577

Cited by 5 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…( 9 ) Progress over the last decade was substantial in that the role of AT inflammation ( 10 ) and the gut microbiome (and related metabolites) evolved as crucial players in the pathogenesis of NAFLD. ( 11,12 ) Furthermore, various dietary components as other gastrointestinal hits with proinflammatory potential have been identified. Finally, genetic pathways also play a role in disease manifestation; and several genetic hits, such as patatin‐like phospholipase domain containing 3, transmembrane 6 superfamily member 2, glucokinase regulator, membrane‐bound O‐acyltransferase domain containing 7, and hydroxysteroid 17‐beta dehydrogenase 13, are involved especially in lipid metabolism.…”

mentioning

confidence: 99%

Multiple Parallel Hits Hypothesis in Nonalcoholic Fatty Liver Disease: Revisited After a Decade

2021

View full text Add to dashboard Cite

mentioning

confidence: 99%

Multiple Parallel Hits Hypothesis in Nonalcoholic Fatty Liver Disease: Revisited After a Decade

2021

View full text Add to dashboard Cite

“…The “Multiple parallel hits” hypothesis holds that lipotoxicity and gene polymorphism, together with alteration of gut microbiota, contribute to the progression of NAFLD ( Tilg et al, 2021 ). Over the last decade, a growing number of studies support that gut microbiota plays a crucial role in the pathogenesis of NAFLD ( Leung et al, 2016 ; Mehal and Loomba, 2019 ). Various degrees of gut microbiota dysbiosis exists in NAFLD patients, and patients with different stages of NAFLD often present with variable microbial signatures.…”

Section: Introductionmentioning

confidence: 99%

Ursodeoxycholic Acid Treatment Restores Gut Microbiota and Alleviates Liver Inflammation in Non-Alcoholic Steatohepatitic Mouse Model

Wang

Chen

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Gut microbiota dysbiosis plays an important role in the progression of non-alcoholic fatty liver disease (NAFLD), and no approved drugs are available for NAFLD treatment. In this study, we aimed to explore the dynamic changes of gut microbiota at the different stages of NAFLD and determine whether ursodeoxycholic acid (UDCA) could improve liver histopathological features of non-alcoholic steatohepatitis (NASH) mice induced by a high-fat high-cholesterol (HFHC) diet and its impact on gut microbiota. 6-week-old male C57BL/6 mice were fed with a HFHC or normal diet for 12, 18, and 24 weeks, respectively, to simulate the different stages of NAFLD. 16s ribosomal RNA genes from mice fecal samples at the different time points were sequenced to evaluate the dynamic changes of the gut microbiota. Then, C57BL/6 mice were fed with a HFHC diet for 24 weeks to establish the NASH model. Different doses of UDCA were administered intragastrically for additional 4 weeks. Normal diet–fed mice were taken as control. Serum samples, liver, and intestine tissues were harvested for biochemical tests and histopathological examinations. 16s ribosomal RNA genes from mice fecal samples were sequenced to assess the structural changes of gut microbiota. HFHC diet–fed mice developed simple steatosis, steatohepatitis, and fibrosis at 12, 18, and 24 weeks, respectively. The profile of gut microbiota dynamically changed with the different stages of NAFLD. NASH mice had significantly higher abundance of Fecalibaculum, Coriobacteriaceae_UCG-002, and Enterorhabdus, and lower abundance of norank_f_Muribaculaceae, Bacteroides, and Alistipes, which were partially restored by UDCA treatment. UDCA treatment significantly attenuated hepatic inflammation of NASH mice as indicated by the sum of ballooning and lobular inflammation of the NALFD activity score (3.2 ± 0.8 vs 1.8 ± 0.8, p = 0.029), and partially restored gut microbiota dysbiosis, and increased the expression of Claudin-1 and ZO-1 in the intestine, but did not activate the suppressed Farnesoid X receptor signal pathway. Conclusions: The gut microbiota dynamically changes with the different stages of NAFLD. UDCA treatment (120 mg/kg) could partially restore gut microbiota, repair gut barrier integrity, and attenuate hepatic inflammation in the NASH mouse model.

show abstract

“…[1][2][3] The gut microbiome has emerged as an area of interest, with recent studies suggesting that disruptions in intestinal microbiota may contribute to the pathogenesis of inflammation-mediated disorders such as obesity and inflammatory bowel disease. [4][5][6][7][8] Emerging data additionally suggest a potential causal relationship between changes in gut microbiota and NAFLD/NASH, although are primarily limited to animal studies. This review aims to summarize current evidence to support this relationship and discuss potential targets for novel NASH therapy.…”

mentioning

confidence: 99%

“…Therapeutic options for biopsy‐proven NASH are limited primarily to medical, endoscopic, and surgical weight loss, as well as NASH‐directed pharmacotherapy, such as vitamin E and pioglitazone 1‐3 . The gut microbiome has emerged as an area of interest, with recent studies suggesting that disruptions in intestinal microbiota may contribute to the pathogenesis of inflammation‐mediated disorders such as obesity and inflammatory bowel disease 4‐8 . Emerging data additionally suggest a potential causal relationship between changes in gut microbiota and NAFLD/NASH, although are primarily limited to animal studies.…”

mentioning

confidence: 99%

NASH and the Gut Microbiome: Implications for New Therapies

Tsay

Lim

2022

Clinical Liver Disease

View full text Add to dashboard Cite

Nonalcoholic steatohepatitis (NASH) is an intermediary between nonalcoholic fatty liver disease (NAFLD) and cirrhosis. With the ongoing obesity epidemic and the accompanying metabolic syndrome, the global incidence and prevalence of NAFLD and NASH has been increasing. 1 Therapeutic options for biopsy-proven NASH are limited primarily to medical, endoscopic, and surgical weight loss, as well as NASH-directed pharmacotherapy, such as vitamin E and pioglitazone. [1][2][3] The gut microbiome has emerged as an area of interest, with recent studies suggesting that disruptions in intestinal microbiota may contribute to the pathogenesis of inflammation-mediated disorders such as obesity and inflammatory bowel disease. [4][5][6][7][8] Emerging data additionally suggest a potential causal relationship between changes in gut microbiota and NAFLD/NASH, although are primarily limited to animal studies. This review aims to summarize current evidence to support this relationship and discuss potential targets for novel NASH therapy.

show abstract

The Intestinal Microbiome, Plasma Metabolome, and Liver Transcriptome: A Conspiracy Driving Hepatic Steatosis

Cited by 5 publications

References 10 publications

Multiple Parallel Hits Hypothesis in Nonalcoholic Fatty Liver Disease: Revisited After a Decade

Multiple Parallel Hits Hypothesis in Nonalcoholic Fatty Liver Disease: Revisited After a Decade

Ursodeoxycholic Acid Treatment Restores Gut Microbiota and Alleviates Liver Inflammation in Non-Alcoholic Steatohepatitic Mouse Model

NASH and the Gut Microbiome: Implications for New Therapies

Contact Info

Product

Resources

About