Human Intestinal Barrier Function in Health and Disease

König, Julia; Wells, Jerry M.; Cani, Patrice D.; García-Ródenas, Clara L.; Macdonald, T.T.; Mercenier, Annick; Whyte, Jacqueline; Troost, Freddy J.; Brummer, R.J.M.

doi:10.1038/ctg.2016.54

Cited by 635 publications

(553 citation statements)

References 187 publications

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“…Based on these observations, the association of intestinal inflammation and gut epithelial barrier dysfunction with the HBP cohort was examined, as many studies showed increased incidence of these with butyrate depletion [39]. We measured I-FABP, LPS, and soluble form of zonulin in plasma, biomarkers for gut epithelial health [40].…”

Section: Resultsmentioning

confidence: 99%

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Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

et al. 2018

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Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut–epithelial barrier function markers and microbiome composition could predict systolic BP (SBP). Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability. Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP. Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001). Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001). The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP. These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans. They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.

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Section: Resultsmentioning

confidence: 99%

“…Damage to this barrier makes the environment less hypoxic, conducive to aerobic bacterial growth [39,48]. Microbial-derived butyrate stabilizes gut epithelial tight junction proteins, depletes oxygen, and activates/stabilizes HIF-1 in epithelial cells [49,50].…”

Section: Resultsmentioning

confidence: 99%

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

et al. 2018

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“…As a consequence, barrier disruption can trigger the development of GI diseases such as inflammatory bowel disease (IBD), celiac disease, and colon cancer [2–5]. Other systemic and metabolic diseases such as type I diabetes can also be influenced by barrier changes [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Epithelial Barrier Function in Gut-Bone Signaling

Rios‐Arce

Collins

Schepper

et al. 2017

Advances in Experimental Medicine and Biology

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The intestinal epithelial barrier plays an essential role in maintaining host homeostasis. The barrier regulates nutrient absorption as well as prevents the invasion of pathogenic bacteria in the host. It is composed of epithelial cells, tight junctions, and a mucus layer. Several factors, such as cytokines, diet, and diseases can affect this barrier. These factors have been shown to increase intestinal permeability, inflammation, and translocation of pathogenic bacteria. In addition, dysregulation of the epithelial barrier can result in inflammatory diseases such as inflammatory bowel disease. Our lab and others have also shown that barrier disruption can have systemic effects including bone loss. In this chapter, we will discuss the current literature to understand the link between intestinal barrier and bone. We will discuss how inflammation, aging, dysbiosis and metabolic diseases can affect intestinal barrier-bone link. In addition, we will highlight the current suggested mechanism between intestinal barrier and bone.

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“…Furthermore, the aetiology of IP is poorly understood, with early research indicating that two aspects, namely pathogenic bacteria and gliadin from gluten, are responsible for triggering IP . Although, recent research suggests that the pathogenesis of IP is multifactorial and different for each individual …”

Section: Introductionmentioning

confidence: 99%

“…Correctly identifying patients at risk of IP may allow for timely testing to determine the potential severity of IP and facilitate access to appropriate treatment interventions if required. Although the full extent of untreated IP remains underexamined, there is a considerable amount of research linking the health and integrity of the intestine to chronic disease . The purpose of this review is to summarise the known risk factors for IP and identify the most significant of these risk factors.…”

Section: Introductionmentioning

confidence: 99%

Risk factors associated with intestinal permeability in an adult population: A systematic review

et al. 2019

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Background Increased intestinal permeability (IP) involves the loss of integrity between the cells of the small intestine. IP has been suggested to contribute to the pathogenesis and exacerbation of many chronic diseases. Many potential risk factors for IP are proposed in contemporary literature. The purpose of this review is to identify the most significant risk factors for IP. Methods A systematic search of literature published up until September 2018 in the PubMed, EMBASE, CINAHL, and Scopus databases was conducted. Results A total of 47 articles met the inclusion criteria. Elevated levels of proinflammatory markers, dyslipidaemia, hyperglycaemia, insulin resistance, anthropometric measurements resembling obesity, advanced disease severity, comorbidity and the consumption of a Western‐style diet were identified as the strongest risk factors for altered intestinal integrity. The risk of IP increases when coupled with a multiple disease state or combined with other environmental risk factors. Furthermore, many of the identified risk factors such as anthropometric measurements and biomarkers were external from intestinal health and rather resembled a metabolic‐like condition. Conclusions This review identified a number of potential risk factors for IP, ranging from biomarkers to anthropometric measurements, demographics, dietary intake and chronic diseases. These risk factors warrant the attention of clinicians and other healthcare providers to aid the identification of potential patients at risk of altered IP. Further research needs to examine whether the identified risk factors are homogeneous with the diagnosis of IP or whether the disease state influences the association.

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Human Intestinal Barrier Function in Health and Disease

Cited by 635 publications

References 187 publications

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

Epithelial Barrier Function in Gut-Bone Signaling

Risk factors associated with intestinal permeability in an adult population: A systematic review

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