Abnormal Gut Microbiota Metabolism Specific for Liver Cirrhosis

Wei, Xiao; Zhao, Jiangtao; Jia, Xiaodong; Zhao, Xiangna; Li, Huan; Lin, Weihua; Feng, Ruo; Yuan, Jing

doi:10.3389/fmicb.2018.03051

Cited by 17 publications

(23 citation statements)

References 19 publications

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“…The changing trend of fecal metabolites in our findings is similar to that found in patients with cirrhosis (Wei et al, 2016;Wei et al, 2018;Yang et al, 2018), implying the association of fecal metabolite alteration with disease development, and not the role of CCl 4 . In the present study, the untargeted fecal metabolomics results revealed that mice with liver fibrosis and cirrhosis were characterized with disturbance of pyrimidine and purine metabolism.…”

Section: Discussionsupporting

confidence: 89%

Dynamic Alterations of the Gut Microbial Pyrimidine and Purine Metabolism in the Development of Liver Cirrhosis

Xiong

Shao

et al. 2022

Front. Mol. Biosci.

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Background: Liver cirrhosis is the common end-stage of liver disease which lacks effective treatment, thus studies to determine prevention targets are an urgent need. The intestinal microbiota (IM) play important roles in modulating liver diseases which are mediated by microbial metabolites. Despite decades of growing microbial studies, whether IM contribute to the development of cirrhosis and the intimate metabolic link remain obscure. Here, we aimed to reveal the dynamic alterations of microbial composition and metabolic signatures in carbon tetrachloride (CCl4)-induced liver cirrhosis mice.Methods: CCl4-treated mice or normal control (NC) were sacrificed (n = 10 per group) after 5 and 15 weeks of intervention. The disease severity was confirmed by Masson’s trichrome or Sirius red staining. Metagenomics sequencing and fecal untargeted metabolomics were performed to evaluate the composition and metabolic function of IM in parallel with the development of cirrhosis.Results: The CCl4-treated mice presented liver fibrosis at 5 weeks and liver cirrhosis at 15 weeks indicated by collagen deposition and pseudo-lobule formation, respectively. Mice with liver cirrhosis showed distinct microbial composition from NC, even in the earlier fibrosis stage. Importantly, both of the liver fibrosis and cirrhosis mice were characterized with the depletion of Deltaproteobacteria (p < 0.05) and enrichment of Akkermansia (p < 0.05). Furthermore, fecal metabolomics revealed distinguished metabolomics profiles of mice with liver fibrosis and cirrhosis from the NC. Notably, pathway enrichment analysis pointed to remarkable disturbance of purine (p < 0.001 at 5 weeks, p = 0.034 at 15 weeks) and pyrimidine metabolic pathways (p = 0.005 at 5 weeks, p = 0.006 at 15 weeks) during the development of liver cirrhosis. Interestingly, the disorders of pyrimidine and purine metabolites like the known microbial metabolites thymidine and 2′-deoxyuridine had already occurred in liver fibrosis and continued in cirrhosis.Conclusion: These novel findings indicated the crucial role of IM-modulated pyrimidine and purine metabolites in the development of liver cirrhosis, which provides microbial targets for disease prevention.

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Section: Discussionsupporting

confidence: 89%

Dynamic Alterations of the Gut Microbial Pyrimidine and Purine Metabolism in the Development of Liver Cirrhosis

Xiong

Shao

et al. 2022

Front. Mol. Biosci.

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“…According to previous studies, the connection between gut balance and menthal/functional well-being receive the name “Gut-Brain Axis”, which is is a complex system that helps the body, decreasing stress\anxiety levels [ 3 - 6 , 19 , 20 ] in addition to improving the host’s immune system [ 6 , 10 ]. This axis involves the functions of the gut with the brain providing good health to the host [ 3 - 6 , 19 , 20 ].…”

Section: Resultsmentioning

confidence: 99%

“…The gut and brain send and receive information through the neural pathways as well as through the blood system [ 3 - 6 , 19 , 20 ]. The gut-brain axis also influences the endocrine functions and nervous system, as well as the of host behavior [ 3 - 6 , 19 , 20 ].…”

Section: Resultsmentioning

confidence: 99%

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Psychobiotic Therapy: Method to Reinforce the Immune System

Magalhães-Guedes

2022

Clin Psychopharmacol Neurosci

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Psychobiotics are probiotic microorganisms that beneficially affect the central nervous system functions mediated by the gut-brain axis, improving the host's immune system. Psychobiotic microorganisms can regulate brain pathways and serotonin production (mood controller). The main microbial genera with psychobiotic characteristics are Lactobacillus, Lactococcus and Bifidobacterium. The daily consumption of psychobiotics is called "Psychobiotic Therapy". Psychobiotic therapy has proven antidepressant/anxiolytic properties. Psychobiotic therapy can be used to boost the host's immune balance against pathogens, for example: virus, bacteria and fungus. Thus, psychobiotic therapy can be a promising strategy to improve and/or maintain the quality of life of people who are healthy or who suffer from anxiety/stress disorders, intestinal dysbiosis and even immunosuppressed people. This is such a hot theme it can surely only be a matter of time for psychobiotic therapy offers an "alternative treatment", but scientific, for people diagnosed with a variety of mental/immunological disorders. Instead of targeting the mind (brain), we could go for the gut. "This new way of looking at mental health linked to gut health is literally looking at health upside down".

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“…Altered gut microbiota leads to changes in overall bile acid levels and specific bile acid metabolites, which contribute to enterohepatic tumorigenesis (Sun et al, 2021). Based on clinical as well as animal studies, it is becoming increasingly evident that the gut microbiota is closely related to the development and progression of NAFLD (Schnabl and Brenner, 2014;Quigley and Monsour, 2015;Leung et al, 2016;Mardinoglu et al, 2018;Wei et al, 2018;Yuan et al, 2019;Aron-Wisnewsky et al, 2020). We therefore speculated that compositional changes in the gut microbiota after DJB contribute to the attenuation of hepatic steatosis in NAFLD.…”

Section: Introductionmentioning

confidence: 99%

The Role of Gut Microbiota in Duodenal-Jejunal Bypass Surgery-Induced Improvement of Hepatic Steatosis in HFD-Fed Rats

Gao

Zhang

Xiao

et al. 2021

Front. Cell. Infect. Microbiol.

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Bariatric surgery including duodenal-jejunal bypass surgery (DJB) improves insulin sensitivity and reduces obesity-associated inflammation. However, the underlying mechanism for such an improvement is still incompletely understood. Our objective was to investigate the role of the gut microbiota in DJB-associated improvement of hepatic steatosis in high fat diet (HFD)-fed rats. To study this, hepatic steatosis was induced in male adult Sprague-Dawley rats by feeding them with a 60% HFD. At 8 weeks after HFD feeding, the rats were subjected to either DJB or sham operation. HFD was resumed 1 week after the surgery for 3 more weeks. In additional groups of animals, feces were collected from HFD-DJB rats at 2 weeks after DJB. These feces were then transplanted to HFD-fed rats without DJB at 8 weeks after HFD feeding. Hepatic steatosis and fecal microbiota were analyzed at 4 weeks after surgery or fecal transplantation. Our results showed that DJB alleviated hepatic steatosis in HFD-fed rats. Fecal microbiota analysis showed that HFD-fed and standard diet-fed rats clustered differently. DJB induced substantial compositional changes in the gut microbiota. The fecal microbiota of HFD-fed rats received fecal transplant from DJB rats overlapped with that of HFD-DJB rats. Treatment of rats with HFD-induced liver lesions by fecal transplant from DJB-operated HFD-fed rats also attenuated hepatic steatosis. Thus, alterations in the gut microbiota after DJB surgery are sufficient to attenuate hepatic steatosis in HFD-fed rats. Targeting the gut microbiota could be a promising approach for preventing or treating human NAFLD.

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Abnormal Gut Microbiota Metabolism Specific for Liver Cirrhosis

Cited by 17 publications

References 19 publications

Dynamic Alterations of the Gut Microbial Pyrimidine and Purine Metabolism in the Development of Liver Cirrhosis

Dynamic Alterations of the Gut Microbial Pyrimidine and Purine Metabolism in the Development of Liver Cirrhosis

Psychobiotic Therapy: Method to Reinforce the Immune System

The Role of Gut Microbiota in Duodenal-Jejunal Bypass Surgery-Induced Improvement of Hepatic Steatosis in HFD-Fed Rats

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