Modulating the Intestinal Microbiota: Therapeutic Opportunities in Liver Disease

Philips, Cyriac Abby; Augustine, Philip; Yerol, Praveen Kumar; Ramesh, Ganesh; Ahamed, Rizwan; Rajesh, Sasidharan; George, Tom; Kumbar, Sandeep

doi:10.14218/jcth.2019.00035

Cited by 35 publications

(32 citation statements)

References 79 publications

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“…Одним из важных патогенетических механизмов развития и прогрессирования НАЖБП и ассоциированных состояний является «кишечнопеченочна я ось», предста вл яюща я собой функционально тесную двустороннюю связь между кишечной микробиотой и печенью. Повышенная кишечная проницаемость, бактериальная транслокация и изменения состава микробиоты кишечника являются важными патогенетическими элементами развития гепатита, инициации фиброзных изменений, формирования цирроза печени и его осложнений [20].…”

Section: этиология и патогенезunclassified

Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version

Лазебник

Голованова

Туркина

et al. 2021

jour

101

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Section: этиология и патогенезunclassified

Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version

Лазебник

Голованова

Туркина

et al. 2021

jour

101

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“…Bacteroides thetaiotaomicron, Proteus vulgaris и Escherichia coli превращают триптофан в индол с помощью триптофаназы [3]. Clostridium sporogenes метаболизирует триптофан в триптамин, индолмолочную (ИМК) и индолпропионовую (ИПК) кислоты.…”

Section: триптофанunclassified

“…Высказывается предположение о том, что бактериальные производные ароматических аминокислот могут выступать в качестве не только терапевтических мишеней или неинвазивных биомаркеров, но и биоактивных агентов для терапии и профилактики НАЖБП. В настоящее время не вызывает сомнений важная роль кишечной микробиоты в патогенезе различных заболеваний [1][2][3], в том числе такого распространенного хронического заболевания, как неалкогольная жировая болезнь печени (НАЖБП) [4][5][6][7]. Первая стадия НАЖБП -стеатоз печени -характеризуется избыточным накоплением липидов (свободных жирных кислот (СЖК), церамидов и холестерина) в виде везикулярных отложений в клетках печени.…”

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The role of bacterial metabolites derived from aromatic amino acids in non-alcoholic fatty liver disease

et al. 2020

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The review deals with the role of aromatic amino acids and their microbial metabolites in the development and progression of non-alcoholic fatty liver disease (NAFLD). Pathological changes typical for NAFLD, as well as abnormal composition and/or functional activity of gut microbiota, results in abnormal aromatic amino acid metabolism. The authors discuss the potential of these amino acids and their bacterial metabolites to produce both negative and positive impact on the main steps of NAFLD pathophysiology, such as lipogenesis and inflammation, as well as on the liver functions through regulation of the intestinal barrier and microbiota-gut-liver axis signaling. The review gives detailed description of the mechanism of biological activity of tryptophan and its derivatives (indole, tryptamine, indole-lactic, indole-propyonic, indole-acetic acids, and indole-3-aldehyde) through the activation of aryl hydrocarbon receptor (AhR), preventing the development of liver steatosis. Bacteria-produced phenyl-alanine metabolites could promote liver steatosis (phenyl acetic and phenyl lactic acids) or, on the contrary, could reduce liver inflammation and increase insulin sensitivity (phenyl propionic acid). Tyramine, para-cumarate, 4-hydroxyphenylacetic acids, being by-products of bacterial catabolism of tyrosine, can prevent NAFLD, whereas para-cresol and phenol accelerate the progression of NAFLD by damaging the barrier properties of intestinal epithelium. Abnormalities in bacterial catabolism of tyrosine, leading to its excess, stimulate fatty acid synthesis and promote lipid infiltration of the liver. The authors emphasize a close interplay between bacterial metabolism of aromatic amino acids by gut microbiota and the functioning of the human body. They hypothesize that microbial metabolites of aromatic amino acids may represent not only therapeutic targets or non-invasive biomarkers, but also serve as bioactive agents for NAFLD treatment and prevention.

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“…The microbiome is defined as the genetic material of all the microbes-bacteria, fungi, protozoa and viruses-that live on and inside the human body. Since the microbiome is located primarily in the gut, it is not surprising that the gut microbiome has been the most studied and has been implicated in a wide variety of human diseases, including Alzheimer's disease, cardiovascular disease, diabetes, arthritis, and cancer [8]. In addition, there is an overwhelming amount of evidence on how the gut microbiome regulates liver function, and consequently, liver diseases, including nonalcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma [9,10].…”

Section: Introductionmentioning

confidence: 99%

The Liver Microbiome Is Implicated in Cancer Prognosis and Modulated by Alcohol and Hepatitis B

Chakladar

Wong

Kuo

et al. 2020

Cancers

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Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world. Previous studies have identified the importance of alcohol and hepatitis B (HBV) infection on HCC carcinogenesis, indicating synergy in the methods by which these etiologies advance cancer. However, the specific molecular mechanism behind alcohol and HBV-mediated carcinogenesis remains unknown. Because the microbiome is emerging as a potentially important regulator of cancer development, this study aims to classify the effects of HBV and alcohol on the intratumoral liver microbiome. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to infer microbial abundance. This abundance was then correlated to clinical variables and to cancer and immune-associated gene expression, in order to determine how microbial abundance may contribute to differing cancer progression between etiologies. We discovered that the liver microbiome is likely oncogenic after exposure to alcohol or HBV, although these etiological factors could decrease the abundance of a few oncogenic microbes, which would lead to a tumor suppressive effect. In HBV-induced tumors, this tumor suppressive effect was inferred based on the downregulation of microbes that induce cancer and stem cell pathways. Alcohol-induced tumors were observed to have distinct microbial profiles from HBV-induced tumors, and different microbes are clinically relevant in each cohort, suggesting that the effects of the liver microbiome may be different in response to different etiological factors. Collectively, our data suggest that HBV and alcohol operate within a normally oncogenic microbiome to promote tumor development, but are also able to downregulate certain oncogenic microbes. Insight into why these microbes are downregulated following exposure to HBV or alcohol, and why the majority of oncogenic microbes are not downregulated, may be critical for understanding whether a pro-tumor liver microbiome could be suppressed or reversed to limit cancer progression.

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Modulating the Intestinal Microbiota: Therapeutic Opportunities in Liver Disease

Cited by 35 publications

References 79 publications

Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version

Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version

The role of bacterial metabolites derived from aromatic amino acids in non-alcoholic fatty liver disease

The Liver Microbiome Is Implicated in Cancer Prognosis and Modulated by Alcohol and Hepatitis B

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