Clinical Effects of Gamma-Radiation-Resistant<i>Aspergillus sydowii</i>on Germ-Free Mice Immunologically Prone to Inflammatory Bowel Disease

Rodriguez-Palacios, Alexander; Aladyshkina, Natalia; Retuerto, Mauricio; Hager, Christopher; Ilić, Sanja; Ghannoum, Mahmoud A.; Cominelli, Fabio

doi:10.1155/2016/5748745

Cited by 8 publications

(5 citation statements)

References 22 publications

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“…SAMP and AKR mice were maintained under SPF conditions, fed with standard laboratory chow, and kept on 12-h light/dark cycles in the animal resource core (ARC) facility of Case Western Reserve University (CWRU). GF SAMP mice have been propagated in our ARC facility at CWRU since 2011 (60,61). All protocols were approved by the institutional animal care and use committee of CWRU.…”

Section: Methodsmentioning

confidence: 99%

Neutralization of IL-1α ameliorates Crohn’s disease-like ileitis by functional alterations of the gut microbiome

Menghini

Corridoni

Buttó

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Crohn’s disease and ulcerative colitis are chronic and progressive inflammatory bowel diseases (IBDs) that are attributed to dysregulated interactions between the gut microbiome and the intestinal mucosa-associated immune system. There are limited studies investigating the role of either IL-1α or IL-1β in mouse models of colitis, and no clinical trials blocking either IL-1 have yet to be performed. In the present study, we show that neutralization of IL-1α by a specific monoclonal antibody against murine IL-1α was highly effective in reducing inflammation and damage in SAMP mice, mice that spontaneously develop a Crohn’s-like ileitis. Anti-mouse IL-1α significantly ameliorated the established, chronic ileitis and also protected mice from developing acute DSS-induced colitis. Both were associated with taxonomic divergence of the fecal gut microbiome, which was treatment-specific and not dependent on inflammation. Anti–IL-1α administration led to a decreased ratio ofProteobacteriatoBacteroidetes, decreased presence ofHelicobacterspecies, and elevated representation ofMucispirillum schaedleriandLactobacillus salivarius. Such modification in flora was functionally linked to the antiinflammatory effects of IL-1α neutralization, as blockade of IL-1α was not effective in germfree SAMP mice. Furthermore, preemptive dexamethasone treatment of DSS-challenged SAMP mice led to changes in flora composition without preventing the development of colitis. Thus, neutralization of IL-1α changes specific bacterial species of the intestinal microbiome, which is linked to its antiinflammatory effects. These functional findings may be of significant value for patients with IBD, who may benefit from targeted IL-1α–based therapies.

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Section: Methodsmentioning

confidence: 99%

Neutralization of IL-1α ameliorates Crohn’s disease-like ileitis by functional alterations of the gut microbiome

Menghini

Corridoni

Buttó

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…For instance, Aspergillus spp. and some species such as Aspergillus sydowii are considered emerging pathogens and have proven to evoke IBD ( 46 ). Therefore, it is reasonable to infer that the infection of microsporidia increased the chances of initiation and development of IBD.…”

Section: Discussionmentioning

confidence: 99%

Microsporidia persistence in host impairs epithelial barriers and increases chances of inflammatory bowel disease

Jin,

Tang,

Cao

et al. 2024

Microbiol Spectr

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Microsporidia are intracellular fungus-like pathogens and the infection symptoms include recurrent diarrhea and systematic inflammations. The major infection route of microsporidia is the digestive tract. Since microsporidia are hard to fully eliminate, the interactions and persistence of the pathogen within epithelium may modulate host susceptibility to digestive disorders. In this study, both in vitro and in vivo infection models were applied. The alterations of epithelial barrier integrity, permeability, and tight junction proteins after microsporidia infection were assessed on MDCK/Caco-2 monolayers. The fecal intestinal microbiota and tissue alterations after microsporidia infection were assessed on C57BL/6 mice. Moreover, the susceptibility to develop dextran sulfate sodium (DSS)-induced inflammatory bowel diseases (IBDs) was also analyzed by the murine infection model. The results demonstrated that microsporidia infection increased epithelium permeability, weakened wound healing capability, and destructed tight junction protein zonula occludens-1. Microsporidia infection also dysregulates intestinal microbiota. These impairing effects of microsporidia increased host vulnerability to develop enteritis as shown by the murine model of DSS-induced IBD. Our study is the first to elucidate molecular mechanisms of the damaging effects of microsporidia on host epithelium and pointed out the cryptic threats of latent microsporidia infection to public health as reflected by the increased chances of developing more severe diseases. IMPORTANCE Microsporidia are widely present in nature and usually cause latent and persistent infections in hosts. Given the fact that the digestive tract is the major infection route, it is of great importance to explore the consequences of microsporidia infection on the intestinal epithelial barrier and the risks to the host. In this study, we demonstrated the destructing effects of microsporidium infection on epithelial barriers manifested as increased epithelial permeability, weakened wound healing ability, and disrupted tight junctions. Moreover, microsporidia made the host more susceptible to dextran sulfate sodium-induced inflammatory bowel disease. These findings provide new evidence for us to better understand and develop novel strategies for microsporidia prevention and disease control.

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“…The innate immune response can be initiated and strengthened by recognizing pathogen-associated molecular patterns (PAMPs) on dislodged organisms through types of pattern recognition receptors (PRRs) on innate cells including C-type lectin receptors, Toll-like receptors, nucleotide-binding oligomerization domain-like receptors and mannose receptors, followed by a cascade of signaling transductions [ 16 , 18 , 22 , 24 , 26 , 30 , 41 – 46 ]. Along with the activated innate immune response, the adaptive immune system is about to be highly motivated and take part in the modulation of IBD, and T subsets (Th1, Th2, Th17, Treg) are the most well-studied cells during the process of IBD [ 19 , 23 , 25 , 39 , 47 – 61 ].…”

Section: Intestinal Flora and Ibdmentioning

confidence: 99%

“…Along with the activated innate immune response, the adaptive immune system is about to be highly motivated and take part in the modulation of IBD, and T subsets (Th1, Th2, Th17, Treg) are the most well-studied cells during the process of IBD [ 19 , 23 , 25 , 39 , 47 – 61 ].…”

Section: Intestinal Flora and Ibdmentioning

confidence: 99%

Updated immunomodulatory roles of gut flora and microRNAs in inflammatory bowel diseases

2022

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Inflammatory bowel disease is a heterogeneous intestinal inflammatory disorder, including ulcerative colitis (UC) and Crohn's disease (CD). Existing studies have shown that the pathogenesis of IBD is closely related to the host's genetic susceptibility, intestinal flora disturbance and mucosal immune abnormalities, etc. It is generally believed that there are complicated interactions between host immunity and intestinal microflora/microRNAs during the occurrence and progression of IBD. Intestinal flora is mainly composed of bacteria, fungi, viruses and helminths. These commensals are highly implicated in the maintenance of intestinal microenvironment homeostasis alone or in combination. MiRNA is an endogenous non-coding small RNA with a length of 20 to 22 nucleotides, which can perform a variety of biological functions by silencing or activating target genes through complementary pairing bonds. A large quantity of miRNAs are involved in intestinal inflammation, mucosal barrier integrity, autophagy, vesicle transportation and other small RNA alterations in IBD circumstance. In this review, the immunomodulatory roles of gut flora and microRNAs are updated in the occurrence and progression of IBD. Meanwhile, the gut flora and microRNA targeted therapeutic strategies as well as other immunomodulatory approaches including TNF-α monoclonal antibodies are also emphasized in the treatment of IBD.

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Clinical Effects of Gamma-Radiation-ResistantAspergillus sydowiion Germ-Free Mice Immunologically Prone to Inflammatory Bowel Disease

Cited by 8 publications

References 22 publications

Neutralization of IL-1α ameliorates Crohn’s disease-like ileitis by functional alterations of the gut microbiome

Neutralization of IL-1α ameliorates Crohn’s disease-like ileitis by functional alterations of the gut microbiome

Microsporidia persistence in host impairs epithelial barriers and increases chances of inflammatory bowel disease

Updated immunomodulatory roles of gut flora and microRNAs in inflammatory bowel diseases

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