Hallmarks of the human intestinal microbiome on liver maturation and function

Almeida, Joana; Tenreiro, Miguel F.; Martínez-Santamaría, Lucía; Guerrero-Aspizua, Sara; Gisbert, Javier P.; Alves, Paula M.; Serra, Margarida; Baptista, Pedro M.

doi:10.1016/j.jhep.2021.10.015

Cited by 17 publications

(14 citation statements)

References 302 publications

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“…Interestingly, it has become apparent that even molecular signals coming from outside the liver could be involved. Indeed, a fundamental role for the gut microbiome as a critical contributor to post-natal hepatic programming and the preservation of adult liver function is increasingly being recognized [4]. Nevertheless, evidence indicates that a core set of TFs interact in the adult liver, regulating each other's expression, restricting cell proliferation and stabilizing the commitment to hepatocyte identity [6,20].…”

Section: Post-natal Hepatic Identity: Cis-regulatory Modules (Cmrs) T...mentioning

confidence: 99%

“…These cells support hepatocellular function, and together with hepatocytes are arranged in threedimensional anatomical units in the form of hexagonal shaped columns called liver lobules [2,3]. Liver lobules are perfused by two sources of blood, portal venous blood which is oxygen-poor but rich in nutrients, toxins and gut microbiota-derived molecules, and oxygenated blood coming from the hepatic artery [2,4]. These afferent blood vessels enter the lobules from the corners of the hexagonal structures, termed the portal nodes, and form capillary-size vessels known as sinusoids which ultimately drain in a central vein.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Loss of liver function in chronic liver disease: An identity crisis

Berasain¹,

Arechederra²,

Argemí³

et al. 2023

Journal of Hepatology

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Section: Post-natal Hepatic Identity: Cis-regulatory Modules (Cmrs) T...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Loss of liver function in chronic liver disease: An identity crisis

Berasain¹,

Arechederra²,

Argemí³

et al. 2023

Journal of Hepatology

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“…Besides the external influences, the bile acid pool is an essential modulator of the gut microbiome and vice versa. 16 , 38 Through the conjugation of secondary bile acids by the microbiota itself, microbial changes in bile acids can lead to altered signaling through bile acid receptors. 7 , 8 Conversely, bile acids emerge to be the major regulator to shape the gut microbiome itself.…”

Section: Discussionmentioning

confidence: 99%

The influence of liver transplantation on the interplay between gut microbiome and bile acid homeostasis in children with biliary atresia

Waldner

Aldrian

Zöggeler

et al. 2023

Hepatology Communications

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Background: Biliary atresia (BA) causes neonatal cholestasis and rapidly progresses into cirrhosis if left untreated. Kasai portoenterostomy may delay cirrhosis. BA remains among the most common indications for liver transplantation (LT) during childhood. Liver function and gut microbiome are interconnected. Disturbed liver function and enterohepatic signaling influence microbial diversity. We, herein, investigate the impact of LT and reestablishment of bile flow on gut microbiome–bile acid homeostasis in children with BA before (pre, n = 10), 3 months (post3m, n = 12), 12 months (post12m, n = 9), and more than 24 months (post24 + m, n = 12) after LT. Methods: We analyzed the intestinal microbiome of BA patients before and after LT by 16S-rRNA-sequencing and bioinformatics analyses, and serum primary and secondary bile acid levels. Results: The gut microbiome in BA patients exhibits a markedly reduced alpha diversity in pre (p = 0.015) and post3m group (p = 0.044), and approximated healthy control groups at later timepoints post12m (p = 1.0) and post24 + m (p = 0.74). Beta diversity analysis showed overall community structure similarities of pre and post3m (p = 0.675), but both differed from the post24 + m (p < 0.001). Longitudinal analysis of the composition of the gut microbiome revealed the Klebsiella genus to show increased abundance in the post24 + m group compared with an age-matched control (p = 0.029). Secondary bile acid production increased 2+ years after LT (p = 0.03). Multivariable associations of microbial communities and clinical metadata reveal several significant associations of microbial genera with tacrolimus and mycophenolate mofetil–based immunosuppressive regimens. Conclusions: In children with BA, the gut microbiome shows strongly reduced diversity before and shortly after LT, and approximates healthy controls at later timepoints. Changes in diversity correlate with altered secondary bile acid synthesis at 2+ years and with the selection of different immunosuppressants.

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“…The gut microbiota and its metabolites involved in hepatic metabolism and inflammation via the gut–liver axis were summarized in our previous review [ 4 ]. In particular, gut microbial metabolites, such as SCFAs and BAs can directly affect hepatic glucose and lipid metabolism [ 25 , 26 , 27 ]. However, the effects of gut microbiota depletion via Abx treatment on hepatic lipid metabolism in mice are not entirely clear yet.…”

Section: Introductionmentioning

confidence: 99%

Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice

Han

Wang

Zhong

et al. 2022

IJMS

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Dysregulated lipid metabolism is a key pathology in metabolic diseases and the liver is a critical organ for lipid metabolism. The gut microbiota has been shown to regulate hepatic lipid metabolism in the host. However, the underlying mechanism by which the gut microbiota influences hepatic lipid metabolism has not been elucidated. Here, a gut microbiota depletion mouse model was constructed with an antibiotics cocktail (Abx) to study the mechanism through which intestinal microbiota regulates hepatic lipid metabolism in high-fat diet (HFD)-fed mice. Our results showed that the Abx treatment effectively eradicated the gut microbiota in these mice. Microbiota depletion reduced the body weight and fat deposition both in white adipose tissue and liver. In addition, microbiota depletion reduced serum levels of glucose, total cholesterol (TC), low-density lipoproteins (LDL), insulin, and leptin in HFD-fed mice. Importantly, the depletion of gut microbiota in HFD-fed mice inhibited excessive hepatic lipid accumulation. Mechanistically, RNA-seq results revealed that gut microbiota depletion changed the expression of hepatic genes involved in cholesterol and fatty acid metabolism, such as Cd36, Mogat1, Cyp39a1, Abcc3, and Gpat3. Moreover, gut microbiota depletion reduced the abundance of bacteria associated with abnormal metabolism and inflammation, including Lachnospiraceae, Coriobacteriaceae_UCG-002, Enterorhabdus, Faecalibaculum, and Desulfovibrio. Correlation analysis showed that there was strong association between the altered gut microbiota abundance and the serum cholesterol level. This study indicates that gut microbiota ameliorates HFD-induced hepatic lipid metabolic dysfunction, which might be associated with genes participating in cholesterol and fatty acid metabolism in the liver.

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Hallmarks of the human intestinal microbiome on liver maturation and function

Cited by 17 publications

References 302 publications

Loss of liver function in chronic liver disease: An identity crisis

Loss of liver function in chronic liver disease: An identity crisis

The influence of liver transplantation on the interplay between gut microbiome and bile acid homeostasis in children with biliary atresia

Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice

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