Indoles: metabolites produced by intestinal bacteria capable of controlling liver disease manifestation

Hendrikx, Tim; Schnabl, Bernd

doi:10.1111/joim.12892

Cited by 131 publications

(101 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This detrimental effect of AUD on the intestinal environment was confirmed by our study. We observed high serum levels of LPS and pro‐inflammatory cytokines/chemokines in the AUD patients compared to the control group as well as a decreased microbial alpha diversity with the prevalence of potentially pathogenic bacteria, such as Enterobacteriaceae, a finding consistent with previous works in human and animal models …”

Section: Discussionsupporting

confidence: 90%

“…We observed high serum levels of LPS and pro-inflammatory cytokines/chemokines in the AUD patients compared to the control group as well as a decreased microbial alpha diversity with the prevalence of potentially pathogenic bacteria, such as Enterobacteriaceae, a finding consistent with previous works in human and animal models. 12,[30][31][32][33][34] We also reported an increased abundance of Collinsella and Prevotella in AUD patients in this study. Because these bacteria can metabolize alcohol, 35 their overgrowth can be induced by prolonged alcohol exposure.…”

Section: Discussionsupporting

confidence: 78%

See 1 more Smart Citation

Gut microbiota compositional and functional fingerprint in patients with alcohol use disorder and alcohol‐associated liver disease

Addolorato

Ponziani

Dionisi

et al. 2020

Liver International

View full text Add to dashboard Cite

Background & aims Alcohol use disorder (AUD) represents the most common cause of liver disease. The gut microbiota plays a critical role in the progression of alcohol‐related liver damage. Aim of this study was to characterize the gut microbial composition and function in AUD patients with alcohol‐associated liver disease (AALD). Methods This study included 36 AUD patients (14 with cirrhosis) who were active drinkers and an equal number of matched controls. Stool microbial composition, serum levels of lipopolysaccharide, cytokines/chemokines and gut microbiota functional profile were assessed. Results AUD patients had a decreased microbial alpha diversity as compared to controls (0.092 vs 0.130, P = .047) and a specific gut microbial signature. The reduction of Akkermansia and the increase in Bacteroides were able to identify AUD patients with an accuracy of 93.4%. Serum levels of lipopolysaccharide (4.91 vs 2.43, P = .009) and pro‐inflammatory mediators (tumour necrosis factor alpha 60.85 vs 15.08, P = .001; interleukin [IL] 1beta 4.43 vs 1.72, P = .0001; monocyte chemoattractant protein 1 225.22 vs 16.43, P = .006; IL6 1.87 vs 1.23, P = .008) were significantly increased in AUD patients compared to controls and in cirrhotic patients compared to non‐cirrhotic ones (IL6 3.74 vs 1.39, P = .019; IL8 57.60 vs 6.53, P = .004). The AUD‐associated gut microbiota showed an increased expression of gamma‐aminobutyric acid (GABA) metabolic pathways and energy metabolism. Conclusions AUD patients present a specific gut microbial fingerprint, associated with increased endotoxaemia, systemic inflammatory status and functional alterations that may be involved in the progression of the AALD and in the pathogenesis of AUD.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 78%

Gut microbiota compositional and functional fingerprint in patients with alcohol use disorder and alcohol‐associated liver disease

Addolorato

Ponziani

Dionisi

et al. 2020

Liver International

View full text Add to dashboard Cite

show abstract

“…49 Detailed pathways of tryptophan metabolism were recently reviewed by Hendrikx and Schnabl. 50 Several bacterial species convert tryptophan into indole and indole derivatives mainly via the enzyme tryptophanase, which is expressed in many gram-negative, as well as gram-positive bacterial species including Escherichia coli, Clostridium spp. and Bacteroides spp.. 51 Diverse indole derivatives, such as indole-3-aldehyde, indole-3-acetic acid, indole-3-propionic acid, indole-3-acetaldehyde, and indole acrylic acid bind and activate the aryl hydrocarbon receptor (AhR).…”

Section: Changes In Microbial Metabolitesmentioning

confidence: 99%

From intestinal dysbiosis to alcohol-associated liver disease

Mendes

Schnabl

2020

Clin Mol Hepatol

View full text Add to dashboard Cite

Alcohol-associated intestinal dysbiosis and bacterial overgrowth can lead to a dysregulation of tryptophan metabolism and lower production of indoles. Several of these indole derivatives are aryl hydrocarbon receptor ligands that, in turn, are involved in antimicrobial defense via induction of interleukin-22 (IL-22). IL-22 increases the expression of intestinal regenerating islet-derived 3 (Reg3) lectins, which maintain low bacterial colonization of the inner mucus layer and reduce bacterial translocation to the liver. Chronic alcohol consumption is associated with reduced intestinal expression of Reg3β and Reg3γ, increased numbers of mucosa-associated bacteria and bacterial translocation. Translocated microbial products and viable bacteria reach the liver and activate the innate immune system. Release of inflammatory molecules promotes inflammation, contributes to hepatocyte death and results in a fibrotic response. This review summarizes the mechanisms by which chronic alcohol intake changes the gut microbiota and contributes to alcohol-associated liver disease by changing microbial-derived metabolites.

show abstract

“…Similarly the indolelactic acid content in the EGs increased 1.9, 1.3, and 1.7 times than that in the CGs at D1, D3, and D5, respectively ( Figure 4b). Indoleacrylic acid and indolelactic acid are tryptophan catabolites that affect various physiological processes (Roager & Licht, 2018), such as inflammation (Wlodarska et al, 2017) and liver disease (Hendrikx & Schnabl, 2019). Thus, the accumulation of indoleacrylic acid and indolelactic acid indicates the potential physiological effect of LJF in the body.…”

Section: Influence Of Ljf On Rat Metabolismmentioning

confidence: 99%

Plasma metabolomics analysis of endogenous and exogenous metabolites in the rat after administration of Lonicerae Japonicae Flos

Chen

et al. 2020

Biomedical Chromatography

View full text Add to dashboard Cite

Lonicerae Japonicae Flos (LJF) is a typical herbal medicine and is used as a functional food. LJF, which has complex chemical compounds, has various biological effects. The global metabolomics, focusing on both the endogenous and exogenous metabolites, have not yet been investigated for LJF in normal healthy rats using LC–MS. In this study, plasma metabolomics was analyzed after the administration of LJF at different time intervals, and the exogenous metabolites were identified. Partial least squares discriminant analysis showed significant differences in chemical content in the dosed rats. Cholic acid, indoleacrylic acid, indolelactic acid, hippuric acid, N‐acetyl‐phenylalanine, and N‐acetyl‐serotonin significantly accumulated in the dosed rats. Lysophosphatidylethanolamine and lysophosphatidylcholine content, including plasmalogen, increased. There were 25 components of LJF, including 15 prototypes and 10 metabolites, that were identified. The 15 prototypes included phenolic acids, flavonoids, and iridoids, and their contents decreased with an increase in the administration time. Glucuronidation and sulfation of polyphenols were found for LJF. The exogenous glucuronide and sulfate metabolites—including dihydrocoumaric acid‐sulfate, dihydrocaffeic acid‐sulfate, dihydroferulic acid‐sulfate, apigenin‐glucuronide, apigenin‐glucuronide‐sulfate, isorhamnetin‐glucuronide‐sulfate, and others—were identified with a neutral loss of 176 and 80, respectively. The metabolic differences found in the study may serve as biomarkers of LJF consumption and promote the understanding of the mechanism of action of LJF.

show abstract

Indoles: metabolites produced by intestinal bacteria capable of controlling liver disease manifestation

Abstract: Hendrikx T, Schnabl B (University of California San Diego, La Jolla; VA San Diego Healthcare System, San Diego, CA, USA). Indoles: metabolites produced by intestinal bacteria capable of controlling liver disease manifestation. J Intern Med (Review). 2019; 286: 32-40.

Cited by 131 publications

References 78 publications

Gut microbiota compositional and functional fingerprint in patients with alcohol use disorder and alcohol‐associated liver disease

Gut microbiota compositional and functional fingerprint in patients with alcohol use disorder and alcohol‐associated liver disease

From intestinal dysbiosis to alcohol-associated liver disease

Plasma metabolomics analysis of endogenous and exogenous metabolites in the rat after administration of Lonicerae Japonicae Flos

Contact Info

Product

Resources

About