Inflammatory Diseases of the Gut

Rohr, Michael; Narasimhulu, Chandrakala Aluganti; Sharma, Deepak; Doomra, Mitsushita; Riad, Aladdin; Naser, Saleh A.; Parthasarathy, S.

doi:10.1089/jmf.2017.0138

Cited by 26 publications

(20 citation statements)

References 161 publications

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“…IBD is a multifactorial immune disorder characterized by chronic inflammation and apoptosis of intestinal cells, which lead to intestinal mucosa damage, oxidative stress, and activation of immune cells with multiple inflammatory mediators ( 48 – 51 ). The soluble factors produced by probiotics, for which the term of “postbiotic” was recently coined, have been reported to alleviate the IBDs ( 22 , 25 , 52 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of the Lactobacillus rhamnosus GG Effector Protein HM0539 on Inflammatory Response Through the TLR4/MyD88/NF-кB Axis

Yang

Lun

et al. 2020

Front. Immunol.

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Inflammatory bowel disease (IBD) is a chronic and relapsing intestinal inflammatory condition with no effective treatment. Probiotics have gained wide attention because of their outstanding advantages in intestinal health issues. In previous studies, a novel soluble protein, HM0539, which is derived from Lactobacillus rhamnosus GG (LGG), showed significant protective effects against murine colitis, but no clear precise mechanism for this effect was provided. In this study, we hypothesized that the protective function of HM0539 might be derived from its modulation of the TLR4/Myd88/NF-κB axis signaling pathway, which is a critical pathway widely involved in the modulation of inflammatory responses. To test this hypothesis, the underlying anti-inflammatory effects and associated mechanisms of HM0539 were determined both in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and in dextran sulfate sodium (DSS)-induced murine colitis. Our results showed that HM0539 inhibited the expression of cyclooxygenase-2 (COX-2) and the expression inducible nitric oxide synthase (iNOS) by down-regulating the activation of their respective promoter, and as a result this inhibited the production of prostaglandin E2 (PGE2) and nitric oxide (NO). Meanwhile, we demonstrated that HM0539 could ultimately modulate the activation of distal NF-κB by reducing the activation of TLR4 and suppressing the transduction of MyD88. However, even though the overexpression of TLR4 or MyD88 obviously reversed the effect of HM0539 on LPS-induced inflammation, HM0539 still retained some anti-inflammatory activity. Consistent with the in vitro findings, we found that HM0539 inhibited to a great extent the production of inflammatory mediators associated with the suppression of the TLR4/Myd88/NF-κB axis activation in colon tissue. In conclusion, HM0539 was shown to be a promising anti-inflammatory agent, at least in part through its down-regulation of the TLR4-MyD88 axis as well as of the downstream MyD88-dependent activated NF-κB signaling, and hence might be considered as a potential therapeutic option for IBD.

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Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of the Lactobacillus rhamnosus GG Effector Protein HM0539 on Inflammatory Response Through the TLR4/MyD88/NF-кB Axis

Yang

Lun

et al. 2020

Front. Immunol.

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“…Inflammatory bowel disease (IBD) . IBD, including ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by chronic inflammation in the gastrointestinal tract influenced by several factors, including genetics, epigenetics, gut microbiota, and the host immune system [ 55 ]. There have been many RCTs evaluating the effects of probiotics in IBD, associated with ample evidence suggesting that altered gut microbiota contribute to the initiation and progression of IBD.…”

Section: Effects Of Probiotics In High-risk Populations With Immunmentioning

confidence: 99%

Probiotics in Autoimmune and Inflammatory Disorders

2018

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Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to impact the immune system, both in vivo and in vitro. This interaction is linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on mechanistic studies in animal models. Microbial–immune system crosstalk has been linked to: short-chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multiorgan inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

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“…Patients with IBD also suffer from other complications, such as intestinal ulceration, rupture, and strictures, leading to the obstruction of the gastrointestinal tract. Moreover, patients with IBD have an increased risk of colon cancer, in addition to other systemic manifestations, which cumulatively result in serious complications that significantly impacts quality of life [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Are Fried Foods Unhealthy? The Dietary Peroxidized Fatty Acid, 13-HPODE, Induces Intestinal Inflammation In Vitro and In Vivo

et al. 2020

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Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder characterized by progressive inflammation and the erosion of the gut mucosa. Although the exact cause of IBD is unknown, multiple factors contribute to its complex pathogenesis. Diet is one such factor and a strong correlation exists between the western-style, high fat diets (HFDs) and IBD incidence rates. In this study, we propose that the peroxidized fatty acid components of HFDs could contribute to inflammation of the gut. The inflammatory nature of peroxidized linoleic acid (13-HPODE), was confirmed in vitro by analyzing pro-inflammatory gene expression in Caco-2 cells via RT-PCR and ELISA. Additionally, peroxide induced apoptosis was tested by Annexin-V fluorescent staining, while permeability was tested by FITC-dextran flux and TEER. The 13-HPODE-induced inflammation of intestinal epithelium was evaluated in vivo by analyzing pro-inflammatory cytokines under acute and chronic conditions after feeding 13-HPODE to C57BL/6J mice. Our data show that 13-HPODE significantly induced pro-inflammatory gene expression of TNF-α and MCP-1 in vitro, most notably in differentiated Caco-2 cells. Further, acute and chronic 13-HPODE treatments of mice similarly induced pro-inflammatory cytokine expression in the epithelium of both the proximal and distal small intestines, resident immune cells in Peyer’s patches and peritoneal macrophages. The results of this study not only confirm the pro-inflammatory properties of peroxidized fats on the gut mucosa, but for the first time demonstrate their ability to differentially induce pro-inflammatory gene expression and influence permeability in the intestinal epithelium and mucosal cells. Collectively, our results suggest that the immunogenic properties of HFD’s in the gut may be partly caused by peroxide derivatives, providing potential insight into how these diets contribute to exacerbations of IBD.

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Inflammatory Diseases of the Gut

Cited by 26 publications

References 161 publications

Inhibitory Effects of the Lactobacillus rhamnosus GG Effector Protein HM0539 on Inflammatory Response Through the TLR4/MyD88/NF-кB Axis

Inhibitory Effects of the Lactobacillus rhamnosus GG Effector Protein HM0539 on Inflammatory Response Through the TLR4/MyD88/NF-кB Axis

Probiotics in Autoimmune and Inflammatory Disorders

Are Fried Foods Unhealthy? The Dietary Peroxidized Fatty Acid, 13-HPODE, Induces Intestinal Inflammation In Vitro and In Vivo

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