Hypoxia and HIF-1 as key regulators of gut microbiota and host interactions

Pral, Laís Passariello; Fachi, José Luís; Corrêa, Renan Oliveira; Colonna, Marco; Vinolo, Marco Aurélio Ramirez

doi:10.1016/j.it.2021.05.004

Cited by 65 publications

(57 citation statements)

References 104 publications

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“…In addition, metabolites produced by probiotics, such as secreted proteins, indole and SCFAs, also protect the intestinal barriers. Butyrate secreted by Clostridium butyricum can promote the expression of hypoxia-inducible factor (HIF-1α) to upregulate the expression of its targeted downstream intestinal JTs, mucin and antimicrobial peptides, and promote intestinal IL-22 secretion, thereby improving the gut barrier and immune function ( Pral et al., 2021 ).The indole-3-lactic acid produced by Bifidobacterium infantis and Lactobacillus reuteri activates the aryl hydrogen receptors (AhRs) of the gut epithelium by increasing their nuclear localization and up-regulating the protein expression of CYP1A1. The activation of AhRs then leads to lL-22 transcription, which can further increase the expression of antimicrobial peptides ( Ehrlich et al., 2018 ; Hou et al., 2021 ).…”

Section: Regulation Mechanism Of Probiotics On Intestinal Barriers Of...mentioning

confidence: 99%

The Role of Probiotics in Alleviating Postweaning Diarrhea in Piglets From the Perspective of Intestinal Barriers

Gong

Jiang

et al. 2022

Front. Cell. Infect. Microbiol.

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Early weaning of piglets is an important strategy for improving the production efficiency of sows in modern intensive farming systems. However, due to multiple stressors such as physiological, environmental and social challenges, postweaning syndrome in piglets often occurs during early weaning period, and postweaning diarrhea (PWD) is a serious threat to piglet health, resulting in high mortality. Early weaning disrupts the intestinal barrier function of piglets, disturbs the homeostasis of gut microbiota, and destroys the intestinal chemical, mechanical and immunological barriers, which is one of the main causes of PWD in piglets. The traditional method of preventing PWD is to supplement piglet diet with antibiotics. However, the long-term overuse of antibiotics led to bacterial resistance, and antibiotics residues in animal products, threatening human health while causing dysbiosis of gut microbiota and superinfection of piglets. Antibiotic supplementation in livestock diets is prohibited in many countries and regions. Regarding this context, finding antibiotic alternatives to maintain piglet health at the critical weaning period becomes a real emergency. More and more studies showed that probiotics can prevent and treat PWD by regulating the intestinal barriers in recent years. Here, we review the research status of PWD-preventing and treating probiotics and discuss its potential mechanisms from the perspective of intestinal barriers (the intestinal microbial barrier, the intestinal chemical barrier, the intestinal mechanical barrier and the intestinal immunological barrier) in piglets.

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Section: Regulation Mechanism Of Probiotics On Intestinal Barriers Of...mentioning

confidence: 99%

The Role of Probiotics in Alleviating Postweaning Diarrhea in Piglets From the Perspective of Intestinal Barriers

Gong

Jiang

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Electron paramagnetic resonance oximetry revealed partial oxygen pressure (pO 2 ) gradient from 59 mm Hg (8%) in the small intestine wall to 22 mm Hg (3%) at the villus apex and <10 mm Hg (2%) in the small intestinal lumen, whereas colon pO 2 is 5–10 mm Hg near the crypt-lumen interface, and 11 (∼2%) and 3 mm Hg (∼0.4%) in the lumen of ascending and sigmoid colon, respectively ( Singhal and Shah, 2020 ). Thus, intestinal cells exist under conditions ranging from mild to pronounced hypoxia, which leads to HIF stabilization and adaptation to hypoxic conditions ( Pral et al, 2021 ). HIF stabilization in physiological hypoxia supports cell metabolism and barrier function of the intestinal epithelium ( Glover et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

HIF-Dependent NFATC1 Activation Upregulates ITGA5 and PLAUR in Intestinal Epithelium in Inflammatory Bowel Disease

et al. 2021

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Intestinal epithelial cells exist in physiological hypoxia, leading to hypoxia-inducible factor (HIF) activation and supporting barrier function and cell metabolism of the intestinal epithelium. In contrast, pathological hypoxia is a common feature of some chronic disorders, including inflammatory bowel disease (IBD). This work was aimed at studying HIF-associated changes in the intestinal epithelium in IBD. In the first step, a list of genes responding to chemical activation of hypoxia was obtained in an in vitro intestinal cell model with RNA sequencing. Cobalt (II) chloride and oxyquinoline treatment of both undifferentiated and differentiated Caco-2 cells activate the HIF-signaling pathway according to gene set enrichment analysis. The core gene set responding to chemical hypoxia stimulation in the intestinal model included 115 upregulated and 69 downregulated genes. Of this set, protein product was detected for 32 genes, and fold changes in proteome and RNA sequencing significantly correlate. Analysis of publicly available RNA sequencing set of the intestinal epithelial cells of patients with IBD confirmed HIF-1 signaling pathway activation in sigmoid colon of patients with ulcerative colitis and terminal ileum of patients with Crohn’s disease. Of the core gene set from the gut hypoxia model, expression activation of ITGA5 and PLAUR genes encoding integrin α5 and urokinase-type plasminogen activator receptor (uPAR) was detected in IBD specimens. The interaction of these molecules can activate cell migration and regenerative processes in the epithelium. Transcription factor analysis with the previously developed miRGTF tool revealed the possible role of HIF1A and NFATC1 in the regulation of ITGA5 and PLAUR gene expression. Detected genes can serve as markers of IBD progression and intestinal hypoxia.

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“…On the other hand, metabolites from the gut microbiota, such as SCFAs, also play a crucial role in combatting enteric pathogen infection. For example, SCFAs can increase O2 consumption by IECs and contribute to intestinal hypoxia, which is important for barrier function and metabolism of IECs (Pral et al, 2021). Previous studies have reported that butyrate could regulate the expression of hypoxiainducible factor-1 (HIF-1) in IECs and promote the production of tight junction proteins and that HIF-1 signaling provided protection in C. difficile-induced colitis (Hirota et al, 2010;Yin et al, 2020).…”

Section: Signals From the Gut Microbiota To Iecsmentioning

confidence: 99%

Crosstalk Between the Gut Microbiota and Epithelial Cells Under Physiological and Infectious Conditions

Zhou

Yuan

Yang

et al. 2022

Front. Cell. Infect. Microbiol.

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The gastrointestinal tract (GIT) is considered the largest immunological organ, with a diverse gut microbiota, that contributes to combatting pathogens and maintaining human health. Under physiological conditions, the crosstalk between gut microbiota and intestinal epithelial cells (IECs) plays a crucial role in GIT homeostasis. Gut microbiota and derived metabolites can compromise gut barrier integrity by activating some signaling pathways in IECs. Conversely, IECs can separate the gut microbiota from the host immune cells to avoid an excessive immune response and regulate the composition of the gut microbiota by providing an alternative energy source and releasing some molecules, such as hormones and mucus. Infections by various pathogens, such as bacteria, viruses, and parasites, can disturb the diversity of the gut microbiota and influence the structure and metabolism of IECs. However, the interaction between gut microbiota and IECs during infection is still not clear. In this review, we will focus on the existing evidence to elucidate the crosstalk between gut microbiota and IECs during infection and discuss some potential therapeutic methods, including probiotics, fecal microbiota transplantation (FMT), and dietary fiber. Understanding the role of crosstalk during infection may help us to establish novel strategies for prevention and treatment in patients with infectious diseases, such as C. difficile infection, HIV, and COVID-19.

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Hypoxia and HIF-1 as key regulators of gut microbiota and host interactions

Cited by 65 publications

References 104 publications

The Role of Probiotics in Alleviating Postweaning Diarrhea in Piglets From the Perspective of Intestinal Barriers

The Role of Probiotics in Alleviating Postweaning Diarrhea in Piglets From the Perspective of Intestinal Barriers

HIF-Dependent NFATC1 Activation Upregulates ITGA5 and PLAUR in Intestinal Epithelium in Inflammatory Bowel Disease

Crosstalk Between the Gut Microbiota and Epithelial Cells Under Physiological and Infectious Conditions

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