Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway

Choi, Ji Hyun; Moon, Chang Mo; Shin, Tae Seop; Kim, Eun Kyoung; McDowell, Andrea; Jo, Min Kyung; Joo, Yang Hee; Kim, Seong Eun; Jung, Hye Kyung; Shim, Ki Nam; Jung, Sung Ae; Kim, Yoon Keun

doi:10.1038/s12276-019-0359-3

Cited by 112 publications

(106 citation statements)

References 57 publications

(56 reference statements)

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“…IL-10 and TGF-β mainly mediate the negative regulation of inflammatory responses by suppressing the production of pro-inflammatory cytokines [ 55 , 56 ]. Similar suppression of pro-inflammatory cytokines and activation of anti-inflammatory cytokines induced by L. paracasei -derived EVs have also been observed with LPS-challenged human colon cancer cells [ 15 ]. Furthermore, several studies have demonstrated that probiotics-derived EVs controlled inflammatory responses by modulating the cytokine production in the host’s immune cells [ 31 , 42 ].…”

Section: Discussionsupporting

confidence: 60%

“…Only recently has it been increasingly interested in the mechanism of EVs secretion by which probiotics and commensal microbiota communicate with the host. Previous studies have revealed that EVs derived from several probiotics and commensal bacteria, such as Bacteroides fragilis [ 42 ], Akkermansia muciniphila [ 43 ], Escherichia coli Nissle 1917 [ 44 ], Bifidobacterium longum [ 45 ] and Lactobacillus paracasei [ 15 ], exerted similar effects as their parental bacteria. Consistent with these studies, we discovered that L. reuteri BBC3 could produce relatively high quantities of EVs, and treatment of broiler chicks with LrEVs reproduced the protective effects of L. reuteri BBC3 on LPS-induced lower performance and intestinal injury and inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Li et al [ 13 ] showed that L. plantarum WCFS1 secreted EVs with an average size of 101 nm. EVs derived from L. acidophilus and L. paracasei have also been isolated and characterized [ 14 , 15 ]. Recently, several studies also demonstrated the existence of EVs in L. reuteri strains [ 14 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Lactobacillus reuteri-derived extracellular vesicles maintain intestinal immune homeostasis against lipopolysaccharide-induced inflammatory responses in broilers

Lin

Wang

et al. 2021

J Animal Sci Biotechnol

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Background Lactobacillus reuteri strains are widely used as probiotics to prevent and treat inflammatory bowel disease by modulating the host’s immune system. However, the underlying mechanisms by which they communicate with the host have not been clearly understood. Bacterial extracellular vesicles (EVs) have been considered as important mediators of host-pathogen interactions, but their potential role in commensals-host crosstalk has not been widely studied. Here, we investigated the regulatory actions of EVs produced by L. reuteri BBC3, a gut-associated commensal bacterium of Black-Bone chicken, in the development of lipopolysaccharide (LPS)-induced intestinal inflammation in a chicken model using both in vivo and in vitro experiments. Results L. reuteri BBC3 produced nano-scale membrane vesicles with the size range of 60–250 nm. Biochemical and proteomic analyses showed that L. reuteri BBC3-derived EVs (LrEVs) carried DNA, RNA and several bioactive proteins previously described as mediators of other probiotics’ beneficial effects such as glucosyltransferase, serine protease and elongation factor Tu. In vivo broiler experiments showed that administration of LrEVs exerted similar effects as L. reuteri BBC3 in attenuating LPS-induced inflammation by improving growth performance, reducing mortality and decreasing intestinal injury. LrEVs suppressed the LPS-induced expression of pro-inflammatory genes (TNF-α, IL-1β, IL-6, IL-17 and IL-8), and improved the expression of anti-inflammatory genes (IL-10 and TGF-β) in the jejunum. LrEVs could be internalized by chicken macrophages. In vitro pretreatment with LrEVs reduced the gene expression of TNF-α, IL-1β and IL-6 by suppressing the NF-κB activity, and enhanced the gene expression of IL-10 and TGF-β in LPS-activated chicken macrophages. Additionally, LrEVs could inhibit Th1- and Th17-mediated inflammatory responses and enhance the immunoregulatory cells-mediated immunosuppression in splenic lymphocytes of LPS-challenged chickens through the activation of macrophages. Finally, we revealed that the reduced content of both vesicular proteins and nucleic acids attenuated the suppression of LrEVs on LPS-induced inflammatory responses in ex vivo experiments, suggesting that they are essential for the LrEVs-mediated immunoregulation. Conclusions We revealed that LrEVs participated in maintaining intestinal immune homeostasis against LPS-induced inflammatory responses in a chicken model. Our findings provide mechanistic insight into how commensal and probiotic Lactobacillus species modulate the host’s immune system in pathogens-induced inflammation.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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Lactobacillus reuteri-derived extracellular vesicles maintain intestinal immune homeostasis against lipopolysaccharide-induced inflammatory responses in broilers

Lin

Wang

et al. 2021

J Animal Sci Biotechnol

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“…these effects seem to be related to multiple mechanisms, such as the reduction of NO‐production and the amelioration of endoplasmic reticulum stress. [ 51 ]…”

Section: Resultsmentioning

confidence: 99%

Probiomimetics—Novel Lactobacillus‐Mimicking Microparticles Show Anti‐Inflammatory and Barrier‐Protecting Effects in Gastrointestinal Models

Kuhn

Koch

Fuhrmann

2020

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and are characterized by an overshooting immune reaction in the gastrointestinal tract (GIT). [2-4] This leads to tissue damage and a variety of symptoms [2,5] such as diarrhea as well as extraintestinal symptoms related to malabsorption of nutrients and an increased risk of cancer. [6-8] To date, there is no causal therapy available for inflammatory diseases of the intestine and long-lasting suppression and avoidance of triggers is usually required. [9] IBD is currently treated with immunosuppressive drugs. However, these drugs may not be effective for every patient because of individual pharmacogenetic differences. [10,11] Moreover, these drugs are also known to cause a number of side effects, including hepatic injuries and an increased susceptibility to infections. [12-14] In the case of celiac disease, the patients are required to maintain a lifelong gluten-free diet, which is difficult to achieve in the typical "western diet" as gluten is contained in a variety of food products, and even very small amounts can trigger an autoimmune reaction. [15] Administration of probiotic bacteria has shown efficacy as an adjuvant therapy in ameliorating the symptoms related to IBDs. [16] According to the World Health Organization, probiotics are defined as "live microorganisms, which when administered in adequate amounts, confer a health benefit on the host." [17] These bacteria, which include gram-positive Lactobacilli and Bifidobacteria as well as some Escherichia coli strains, have demonstrated multiple beneficial effects, such as modulation of the host immune system, improvement in the epithelial barrier function, and affecting the balance of the various bacterial strains in the gut. [18] Despite the promising potential of probiotics, they are still not always suitable for use as therapeutic agents because of their ability to proliferate. Especially, in the case of patients who take immunosuppressants for long-term control of IBD, the concomitant use of probiotics is not recommended as it can lead to bacteremia and sepsis. [19] A study reported that Escherichia coli Nissle 1917-a strain commonly used as probiotics-possessed the same genes responsible for pathogenicity as detected in other E. coli strains. [18] Once these silent genes are activated by unknown triggers, they may potentially cause pathogenic effects in patients, thus substantially limiting the safety of the probiotics. In this study, we explored the approach of designing therapeutics based on bacterial membrane vesicles (MVs), There is a lack of efficient therapies to treat increasingly prevalent autoimmune diseases, such as inflammatory bowel disease and celiac disease. Membrane vesicles (MVs) isolated from probiotic bacteria have shown tremendous potential for treating intestinal inflammatory diseases. However, possible dilution effects and rapid elimination in the gastrointestinal tract may impair their application. A cell-free and anti-inflammatory therapeutic system-probiomimetics-based on MVs of probiotic bacteria (Lactobacillus casei and Lactobaci...

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“…Prevalence of Fusobacterium activates UPR and promotes inflammation in UC patients (72). Probiotic bacteria such as Lactobacillus paracasei ameliorated intestinal inflammation through ER stress-UPR pathway (73). On the contrary, Lactobacillus acidophilus mitigated intestinal inflammation by suppressing NF-kB and thereby inhibiting ER stress (74).…”

Section: Microbiota Er Stress and Inflammationmentioning

confidence: 99%

Endoplasmic Reticulum Stress and Intestinal Inflammation: A Perilous Union

2020

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The intestinal tract encompasses the largest mucosal surface fortified with a fine layer of intestinal epithelial cells along with highly sophisticated network of the lamina propria immune cells that are indispensable to sustain gut homeostasis. However, it can be challenging to uphold homeostasis when these cells in the intestine are perpetually exposed to insults of both endogenous and exogenous origin. The complex networking and dynamic microenvironment in the intestine demand highly functional cells ultimately burdening the endoplasmic reticulum (ER) leading to ER stress. Unresolved ER stress is one of the primary contributors to the pathogenesis of inflammatory bowel diseases (IBD). Studies also suggest that ER stress can be the primary cause of inflammation and/or the consequence of inflammation. Therefore, understanding the patterns of expression of ER stress regulators and deciphering the intricate interplay between ER stress and inflammatory pathways in intestinal epithelial cells in association with lamina propria immune cells contribute toward the development of novel therapies to tackle IBD. This review provides imperative insights into the molecular markers involved in the pathogenesis of IBD by potentiating ER stress and inflammation and briefly describes the potential pharmacological intervention strategies to mitigate ER stress and IBD. In addition, genetic mutations in the biomarkers contributing to abnormalities in the ER stress signaling pathways further emphasizes the relevance of biomarkers in potential treatment for IBD.

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Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway

Cited by 112 publications

References 57 publications

Lactobacillus reuteri-derived extracellular vesicles maintain intestinal immune homeostasis against lipopolysaccharide-induced inflammatory responses in broilers

Lactobacillus reuteri-derived extracellular vesicles maintain intestinal immune homeostasis against lipopolysaccharide-induced inflammatory responses in broilers

Probiomimetics—Novel Lactobacillus‐Mimicking Microparticles Show Anti‐Inflammatory and Barrier‐Protecting Effects in Gastrointestinal Models

Endoplasmic Reticulum Stress and Intestinal Inflammation: A Perilous Union

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