Cross-talk between bile acids and intestinal microbiota in host metabolism and health

Nie, Yangfan; Hu, Jun; Yan, Xianghua

doi:10.1631/jzus.b1400327

Cited by 107 publications

(100 citation statements)

References 85 publications

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“…To our knowledge, this is the first reported observation that LCA induces autophagy in human (prostate) cancer cells, although a link between bile acids and autophagy has been recently proposed via activation of the farnesoid X receptor (FXR) (Nie, Hu & Yan, 2015). The FXR is a cytoplasmic receptor and an important target for hydrophilic primary bile acids, but is unlikely to play a large role in the biological effects of LCA, which is very hydrophobic and remains almost entirely outside the cell (Goldberg et al, 2013).…”

Section: Discussionmentioning

confidence: 97%

Lithocholic acid induces endoplasmic reticulum stress, autophagy and mitochondrial dysfunction in human prostate cancer cells

Gafar

Draz

Goldberg

et al. 2016

PeerJ

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Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells. LCA induced ER stress-related proteins, such as CCAAT-enhancer-binding protein homologous protein (CHOP), and the phosphorylation of eukaryotic initiation factor 2-alpha (p-eIF2α) and c-Jun N-terminal kinases (p-JNK) in both cancer cell-types. The p53 upregulated modulator of apoptosis (PUMA) and B cell lymphoma-like protein 11 (BIM) levels were decreased at overtly toxic LCA concentrations, although PUMA levels increased at lower LCA concentrations in both cell lines. LCA induced autophagy-related conversion of microtubule-associated proteins 1A/1B light chain 3B (LC3BI–LC3BII), and autophagy-related protein ATG5 in PC-3 cells, but not in autophagy-deficient DU-145 cells. LCA (>10 µM) increased levels of reactive oxygen species (ROS) concentration-dependently in PC-3 cells, whereas ROS levels were not affected in DU-145 cells. Salubrinal, an inhibitor of eIF2α dephosphorylation and ER stress, reduced LCA-induced CHOP levels slightly in PC-3, but not DU-145 cells. Salubrinal pre-treatment increased the cytotoxicity of LCA in PC-3 and DU-145 cells and resulted in a statistically significant loss of cell viability at normally non-toxic concentrations of LCA. The late-stage autophagy inhibitor bafilomycin A1 exacerbated LCA toxicity at subtoxic LCA concentrations in PC-3 cells. The antioxidant α-tocotrienol strongly inhibited the toxicity of LCA in PC-3 cells, but not in DU-145 cells. Collectively, although LCA induces autophagy and ER stress in PC-3 cells, these processes appear to be initially of protective nature and subsequently consequential to, but not critical for the ROS-mediated mitochondrial dysfunction and cytotoxicity of LCA. The full mechanism of LCA-induced mitochondrial dysfunction and cytotoxicity in the similarly sensitive DU-145 cells remains to be elucidated.

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Section: Discussionmentioning

confidence: 97%

Lithocholic acid induces endoplasmic reticulum stress, autophagy and mitochondrial dysfunction in human prostate cancer cells

Gafar

Draz

Goldberg

et al. 2016

PeerJ

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“…Gut microbiota also participate in the production of bioactive metabolites such as BAs that signal through their cognate receptors to regulate the host metabolism . The oxidation of cholesterol to a primary BA in the liver is mediated by cytochrome P‐450 enzymes .…”

Section: Dna Damagementioning

confidence: 99%

Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability

Kompella

Vásquez

2019

Molecular Carcinogenesis

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Obesity, defined as a state of positive energy balance with a body mass index exceeding 30 kg/m2 in adults and 95th percentile in children, is an increasing global concern. Approximately one‐third of the world's population is overweight or obese, and in the United States alone, obesity affects one in six children. Meta‐analysis studies suggest that obesity increases the likelihood of developing several types of cancer, and with poorer outcomes, especially in children. The contribution of obesity to cancer risk requires a better understanding of the association between obesity‐induced metabolic changes and its impact on genomic instability, which is a major driving force of tumorigenesis. In this review, we discuss how molecular changes during adipose tissue dysregulation can result in oxidative stress and subsequent DNA damage. This represents one of the many critical steps connecting obesity and cancer since oxidative DNA lesions can result in cancer‐associated genetic instability. In addition, the by‐products of the oxidative degradation of lipids (e.g., malondialdehyde, 4‐hydroxynonenal, and acrolein), and gut microbiota‐mediated secondary bile acid metabolites (e.g., deoxycholic acid and lithocholic acid), can function as genotoxic agents and tumor promoters. We also discuss how obesity can impact DNA repair efficiency, potentially contributing to cancer initiation and progression. Finally, we outline obesity‐related epigenetic changes and identify the gaps in knowledge to be addressed for the development of better therapeutic strategies for the prevention and treatment of obesity‐related cancers.

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“…Intestinal microbiota can convert primary bile acids into secondary bile acids. The latter, in turn, interacts with mitochondria through farnesoid X receptor (FXR) and G-coupled membrane protein 5 (TGR5) [58]. These transcription factors regulate other proteins that are involved in fatty acid uptake and oxidation, such as peroxisome proliferator-activated receptor alpha (PPAR-α) and steroid response element binding protein 1-c (SREBP-1c) [59].…”

Section: Bile Acidsmentioning

confidence: 99%

Colon epithelial cells luminal environment and physiopathological consequences: impact of nutrition and exercise

Blachier

Resende

Leite

et al. 2018

Nutrire

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The colonic epithelial cells represent a border between the colon luminal content, containing notably bacteria and a complex mixture of compounds, and the "milieu interieur" as defined by the French physiologist Claude Bernard. The physical-chemical composition of the luminal content, including luminal pH and bacterial metabolite, that obviously is not constant, is modified for instance according to the diet. Data obtained recently indicate that physical exercise may also modify the colonic luminal content. Evidence has indicated that modification of the luminal content characteristics has, indeed, consequences for the colonic epithelial cells, notably in terms of energy metabolism and DNA integrity. Although such alterations impact presumably the homeostatic process of the colonic epithelium renewal and the epithelial barrier function, their contribution to pathological processes like mucosal inflammation, pre-neoplasia, and neoplasia remains partly elusive. Open questions remain regarding the individual and collective roles of luminal changes, particularly in a long-term perspective. These questions are related particularly to the capacity of the bacterial metabolites to cross the mucus layer before entering the colonocytes, to the concentrations of metabolites in proximity of the colonic crypt stem cells, and to the capacity of colonocytes to detoxicate deleterious compounds, to take up and utilize beneficial compounds.

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Cross-talk between bile acids and intestinal microbiota in host metabolism and health

Cited by 107 publications

References 85 publications

Lithocholic acid induces endoplasmic reticulum stress, autophagy and mitochondrial dysfunction in human prostate cancer cells

Lithocholic acid induces endoplasmic reticulum stress, autophagy and mitochondrial dysfunction in human prostate cancer cells

Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability

Colon epithelial cells luminal environment and physiopathological consequences: impact of nutrition and exercise

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