Increased Small Intestinal Permeability during Severe Acute Exacerbations of COPD

Intestinal epithelial cell derived alkaline phosphatase (IAP) dephosphorylates/detoxifies bacterial endotoxin lipopolysaccharide (LPS) in the gut lumen. We have earlier demonstrated that consumption of high‐fat high‐cholesterol containing western type‐diet (WD) significantly reduces IAP activity, increases intestinal permeability leading to increased plasma levels of LPS and glucose intolerance. Furthermore, oral supplementation with curcumin that increased IAP activity improved intestinal barrier function as well as glucose tolerance. To directly test the hypothesis that targeted increase in IAP would protect against WD‐induced metabolic consequences, we developed intestine‐specific IAP transgenic mice where expression of human chimeric IAP is under the control of intestine‐specific villin promoter. This chimeric human IAP contains domains from human IAP and human placental alkaline phosphatase, has a higher turnover number, narrower substrate specificity, and selectivity for bacterial LPS. Chimeric IAP was specifically and uniformly overexpressed in these IAP transgenic (IAPTg) mice along the entire length of the intestine. While IAP activity reduced from proximal P1 segment to distal P9 segment in wild‐type (WT) mice, this activity was maintained in the IAPTg mice. Dietary challenge with WD impaired glucose tolerance in WT mice and this intolerance was attenuated in IAPTg mice. Significant decrease in fecal zonulin, a marker for intestinal barrier dysfunction, in WD fed IAPTg mice and a corresponding decrease in translocation of orally administered nonabsorbable 4 kDa FITC dextran to plasma suggests that IAP overexpression improves intestinal barrier function. Thus, targeted increase in IAP activity represents a novel strategy to improve WD‐induced intestinal barrier dysfunction and glucose intolerance.

show abstract

“…), COPD (Sprooten et al. ), Parkinson's disease (Schwiertz et al. ), multiple sclerosis (Buscarinu et al.…”

Section: Discussionmentioning

confidence: 99%

Intestine-specific expression of human chimeric intestinal alkaline phosphatase attenuates Western diet-induced barrier dysfunction and glucose intolerance

Ghosh

Wang

et al. 2018

Physiol Rep

View full text Add to dashboard Cite

show abstract

“…The fact that patients with genetic mannose binding lectin deficiency exhibit a more diverse pulmonary microbiota and a lower risk of exacerbation suggests not only association but also causality (Dicker et al, 2018). Besides the lung flora, the gut microbiota is involved in exacerbations, as suggested by the increased gastrointestinal permeability in patients admitted for COPD exacerbations (Sprooten et al, 2018). Whatever the permeability's origin (hypoxemia or proinflammatory status), the level of circulating gut microbiotadependent trimethylamine-N-oxide has been associated with mortality in COPD patients (Ottiger et al, 2018).…”

Section: Chronic Respiratory Diseasesmentioning

confidence: 99%

The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks

Enaud

Prével

Ciarlo

et al. 2020

Front. Cell. Infect. Microbiol.

419

347

View full text Add to dashboard Cite

The gut and lungs are anatomically distinct, but potential anatomic communications and complex pathways involving their respective microbiota have reinforced the existence of a gut-lung axis (GLA). Compared to the better-studied gut microbiota, the lung microbiota, only considered in recent years, represents a more discreet part of the whole microbiota associated to human hosts. While the vast majority of studies focused on the bacterial component of the microbiota in healthy and pathological conditions, recent works have highlighted the contribution of fungal and viral kingdoms at both digestive and respiratory levels. Moreover, growing evidence indicates the key role of inter-kingdom crosstalks in maintaining host homeostasis and in disease evolution. In fact, the recently emerged GLA concept involves host-microbe as well as microbe-microbe interactions, based both on localized and long-reaching effects. GLA can shape immune responses and interfere with the course of respiratory diseases. In this review, we aim to analyze how the lung and gut microbiota influence each other and may impact on respiratory diseases. Due to the limited knowledge on the human virobiota, we focused on gut and lung bacteriobiota and mycobiota, with a specific attention on inter-kingdom microbial crosstalks which are able to shape local or long-reached host responses within the GLA.

show abstract

“…While this is beyond the scope of this review, the reader is directed to the following reviews for more information on the pathophysiology and immunopathology of these diseases ( 23 – 26 ). It is well-known that the intestinal epithelium is readily damaged in IBD ( 27 ), and increased intestinal permeability has now also been reported in COPD ( 28 , 29 ). Whilst the association between IBD and COPD has been largely investigated at an epidemiological level, further research is required to elucidate the inflammatory mechanisms that link the intestine and the lung.…”

Section: Chronic Inflammatory Diseasesmentioning

confidence: 99%

Links Between Inflammatory Bowel Disease and Chronic Obstructive Pulmonary Disease

et al. 2020

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the gastrointestinal and respiratory tracts, respectively. These mucosal tissues bear commonalities in embryology, structure and physiology. Inherent similarities in immune responses at the two sites, as well as overlapping environmental risk factors, help to explain the increase in prevalence of IBD amongst COPD patients. Over the past decade, a tremendous amount of research has been conducted to define the microbiological makeup of the intestine, known as the intestinal microbiota, and determine its contribution to health and disease. Intestinal microbial dysbiosis is now known to be associated with IBD where it impacts upon intestinal epithelial barrier integrity and leads to augmented immune responses and the perpetuation of chronic inflammation. While much less is known about the lung microbiota, like the intestine, it has its own distinct, diverse microflora, with dysbiosis being reported in respiratory disease settings such as COPD. Recent research has begun to delineate the interaction or crosstalk between the lung and the intestine and how this may influence, or be influenced by, the microbiota. It is now known that microbial products and metabolites can be transferred from the intestine to the lung via the bloodstream, providing a mechanism for communication. While recent studies indicate that intestinal microbiota can influence respiratory health, intestinal dysbiosis in COPD has not yet been described although it is anticipated since factors that lead to dysbiosis are similarly associated with COPD. This review will focus on the gut-lung axis in the context of IBD and COPD, highlighting the role of environmental and genetic factors and the impact of microbial dysbiosis on chronic inflammation in the intestinal tract and lung.

show abstract

Increased Small Intestinal Permeability during Severe Acute Exacerbations of COPD

Cited by 45 publications

References 58 publications

Intestine-specific expression of human chimeric intestinal alkaline phosphatase attenuates Western diet-induced barrier dysfunction and glucose intolerance

Intestine-specific expression of human chimeric intestinal alkaline phosphatase attenuates Western diet-induced barrier dysfunction and glucose intolerance

The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks

Links Between Inflammatory Bowel Disease and Chronic Obstructive Pulmonary Disease

Contact Info

Product

Resources

About