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      Paraprobiotics and Postbiotics of Probiotic Lactobacilli, Their Positive Effects on the Host and Action Mechanisms: A Review

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          Abstract

          Lactobacilli comprise an important group of probiotics for both human and animals. The emerging concern regarding safety problems associated with live microbial cells is enhancing the interest in using cell components and metabolites derived from probiotic strains. Here, we define cell structural components and metabolites of probiotic bacteria as paraprobiotics and postbiotics, respectively. Paraprobiotics and postbiotics produced from Lactobacilli consist of a wide range of molecules including peptidoglycans, surface proteins, cell wall polysaccharides, secreted proteins, bacteriocins, and organic acids, which mediate positive effect on the host, such as immunomodulatory, anti-tumor, antimicrobial, and barrier-preservation effects. In this review, we systematically summarize the paraprobiotics and postbiotics derived from Lactobacilli and their beneficial functions. We also discuss the mechanisms underlying their beneficial effects on the host, and their interaction with the host cells. This review may boost our understanding on the benefits and molecular mechanisms associated with paraprobiotics and probiotics from Lactobacilli, which may promote their applications in humans and animals.

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          The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

          Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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            Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.

            Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.
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              Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism

              ABSTRACT The formation of SCFA is the result of a complex interplay between diet and the gut microbiota within the gut lumen environment. The discovery of receptors, across a range of cell and tissue types for which short chain fatty acids SCFA appear to be the natural ligands, has led to increased interest in SCFA as signaling molecules between the gut microbiota and the host. SCFA represent the major carbon flux from the diet through the gut microbiota to the host and evidence is emerging for a regulatory role of SCFA in local, intermediary and peripheral metabolism. However, a lack of well-designed and controlled human studies has hampered our understanding of the significance of SCFA in human metabolic health. This review aims to pull together recent findings on the role of SCFA in human metabolism to highlight the multi-faceted role of SCFA on different metabolic systems.
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                Author and article information

                Contributors
                Journal
                Front Nutr
                Front Nutr
                Front. Nutr.
                Frontiers in Nutrition
                Frontiers Media S.A.
                2296-861X
                22 October 2020
                2020
                : 7
                : 570344
                Affiliations
                [1] 1China-Norway Joint Lab on Fish Gastrointestinal Microbiota, Feed Research Institute, Chinese Academy of Agricultural Sciences , Beijing, China
                [2] 2Tigray Agricultural Research Institute , Mekelle, Ethiopia
                [3] 3AgricultureIsLife/EnvironmentIsLife and Precision Livestock and Nutrition Unit, AgroBioChem/TERRA, Gembloux Agro-Bio Tech, University of Liege, Passage des Deportes , Gembloux, Belgium
                [4] 4Norway-China Fish Gastrointestinal Microbiota Joint Lab, Institute of Biology, Norwegian University of Science and Technology , Trondheim, Norway
                [5] 5Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences , Beijing, China
                Author notes

                Edited by: Haruki Kitazawa, Tohoku University, Japan

                Reviewed by: Muhammad Shahid Riaz Rajoka, Shenzhen University, China; Xi Ma, China Agricultural University, China

                *Correspondence: Zhigang Zhou zhouzhigang03@ 123456caas.cn

                This article was submitted to Nutritional Immunology, a section of the journal Frontiers in Nutrition

                †These authors have contributed equally to this work

                Article
                10.3389/fnut.2020.570344
                7642493
                33195367
                991ebfa5-d143-41ca-8ae3-757c94a6b266
                Copyright © 2020 Teame, Wang, Xie, Zhang, Yang, Ding, Gao, Olsen, Ran and Zhou.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 June 2020
                : 28 August 2020
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 227, Pages: 16, Words: 13244
                Categories
                Nutrition
                Review

                paraprobiotics,postbiotics,lactobacilli,metabolites,immunomodulatory effect

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