Gut Microbiome and Inflammation: A Study of Diabetic Inflammasome-Knockout Mice

Pahwa, Roma; Balderas, Miriam; Jialal, Ishwarlal; Chen, Xinpu; Luna, Ruth Ann; Devaraj, Sridevi

doi:10.1155/2017/6519785

Cited by 88 publications

(113 citation statements)

References 24 publications

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“…The microbiome, the collective genome of all the microbiota, can have a major influence on the immune system in the gastrointestinal (GI) tract and lung. Imbalances in microbiota composition (dysbiosis) have been associated with many inflammatory conditions, including inflammatory bowel disease (IBD) in the GI tract, 1–3 and chronic obstructive pulmonary disease (COPD) and asthma in the lung as well as other systemic and metabolic diseases (e.g., gout, liver disease, obesity, type II diabetes, and psychologic disorders), 4–12 and even in cardiovascular health and diseases (reviewed in Ref. 13 ).…”

Section: Introductionmentioning

confidence: 99%

The role of the microbiome and the NLRP3 inflammasome in the gut and lung

Donovan

Liu

Shen

et al. 2020

Journal of Leukocyte Biology

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The nucleotide‐binding oligomerization domain (NOD)‐like receptor (NLR) family, pyrin domain‐containing protein 3 (NLRP3) inflammasome, is one of the most well‐characterized inflammasomes, activated by pathogen‐associated molecular patterns and damage‐associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut–lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut–lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.

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Section: Introductionmentioning

confidence: 99%

The role of the microbiome and the NLRP3 inflammasome in the gut and lung

Donovan

Liu

Shen

et al. 2020

Journal of Leukocyte Biology

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“…The pro-in ammatory viral and bacterial pathogens cause typically disruption of TJs and result in dysfunction of gut barrier due to the loss of enterocyte microvilli [35]. Previous studies have shown that the increased Bacteroidetes is associated with dysfunction of innate immune system, resulting in host present in a pro-inflammation state [36], while de ciency of Lactobacillus spp. is involved in gut in ammation and bacterial infection [37].…”

Section: Discussionmentioning

confidence: 99%

Age-Related Changes in the Gut Microbiota Promote Atrial Fibrillation

Zhang¹,

Zhang²,

Luo³

et al. 2020

Preprint

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Background: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-associated diseases. However, whether age-associated gut microbial dysbiosis contributes to AF is still unknown. The aim of this study was to evaluate the effect of gut microbiota on the susceptibility of aging-induced AF and to elucidate the underlying mechanisms. Results: The gut microbiota profiling of fecal samples in aged (22-24 months old) and young (2-3 months old) rats was performed by 16S ribosomal RNA gene analysis. A rat model of fecal microbiota transplantation (FMT) was established for analyzing the possible role of age-associated gut microbial dysbiosis in AF. Here, we found that aging process led to marked shift of the microbiota spectrum. The microbiota in young rats following FMT resembled that of aged microbiota and transmitted the increased AF susceptibility by elevation of circulating lipopolysaccharide (LPS). The mechanism for LPS-driven atrial pro-arrhythmic action was dependent on the activation of atrial nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing (NLRP3)-inflammasome. Inhibition of inflammasome by MCC950 resulted in lower atrial fibrosis and AF susceptibility. In addition, atrial fibrosis, plasma LPS concentration, plasma glucose to oral glucose tolerance test (OGTT), intestinal permeability, and gut pathology were significantly increased in elderly human subjects. Finally, altering the microbiota in aged recipient to resemble that of young restored the intestinal barrier dysfunction and LPS and impaired glucose tolerance, and the worse outcomes of aged dysbiosis on atrial fibrosis and AF susceptibility were abrogated. Conclusions: These data suggest that age-associated microbial dysbiosis induces circulating LPS and impairs glucose tolerance, and thereby promotes AF susceptibility through enhanced activity of atrial NLRP3-inflammasome.

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“…NLRP3-deficient mice had altered interactions between the intestinal microbiome and the host, which may influence the progression of symptoms associated with metabolic syndromes. Furthermore, low-grade intestinal lesions were present in these NLRP3-deficient mice that depended on excessive growth of Prevotellaceae and Bacteroidetes [116], and the ratio of Firmicutes to Bacteroidetes was decreased [120]. CCL5 is caused by bacterial and viral infections and recruits a variety of innate and adaptive immune cells by activating toll-like receptors on epithelial cells [121].…”

Section: Nlrp3 and The Microbiomementioning

confidence: 99%

Modulatory Mechanisms of the NLRP3 Inflammasomes in Diabetes

et al. 2019

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The inflammasome is a multiprotein complex that acts to enhance inflammatory responses by promoting the production and secretion of key cytokines. The best-known inflammasome is the NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome. The evidence has shown that the NLRP3 inflammasome, IL-1β, thioredoxin-interacting protein (TXNIP), and pyroptosis play vital roles in the development of diabetes. This review summarizes the regulation of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) by NLRP3 via modulation of glucose tolerance, insulin resistance, inflammation, and apoptosis mediated by endoplasmic reticulum stress in adipose tissue. Moreover, NLRP3 participates in intestinal homeostasis and inflammatory conditions, and NLRP3-deficient mice experience intestinal lesions. The diversity of an individual’s gut microbiome and the resultant microbial metabolites determines the extent of their involvement in the physiological and pathological mechanisms within the gut. As such, further study of the interaction between the NLRP3 inflammasome and the complex intestinal environment in disease development is warranted to discover novel therapies for the treatment of diabetes.

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Gut Microbiome and Inflammation: A Study of Diabetic Inflammasome-Knockout Mice

Cited by 88 publications

References 24 publications

The role of the microbiome and the NLRP3 inflammasome in the gut and lung

The role of the microbiome and the NLRP3 inflammasome in the gut and lung

Age-Related Changes in the Gut Microbiota Promote Atrial Fibrillation

Modulatory Mechanisms of the NLRP3 Inflammasomes in Diabetes

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