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      The metabolites of lactic acid bacteria: classification, biosynthesis and modulation of gut microbiota

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      Author(s): 1 , 2 , 1 , 2 , 1 , 2 , 3 , 4 , 5 , * ,
      Publication date (Electronic, pub):
      Publication date (Electronic, collection):
      Journal: Microbial Cell
      Publisher: Shared Science Publishers OG
      Keywords: metabolites, lactic acid bacteria, gut microbiota, immune system

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          Abstract

          Lactic acid bacteria (LAB) are ubiquitous microorganisms that can colonize the intestine and participate in the physiological metabolism of the host. LAB can produce a variety of metabolites, including organic acids, bacteriocin, amino acids, exopolysaccharides and vitamins. These metabolites are the basis of LAB function and have a profound impact on host health. The intestine is colonized by a large number of gut microorganisms with high species diversity. Metabolites of LAB can keep the balance and stability of gut microbiota through aiding in the maintenance of the intestinal epithelial barrier, resisting to pathogens and regulating immune responses, which further influence the nutrition, metabolism and behavior of the host. In this review, we summarize the metabolites of LAB and their influence on the intestine. We also discuss the underlying regulatory mechanisms and emphasize the link between LAB and the human gut from the perspective of health promotion.

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          Diversity of the human intestinal microbial flora.

          Paul Eckburg, Elisabeth Bik, Charles Bernstein … (2005)
          The human endogenous intestinal microflora is an essential "organ" in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.
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            Metabolic regulation of gene expression by histone lactylation

            Di Zhang, Zhanyun Tang, He Huang … (2019)
            The Warburg effect, originally describing augmented lactogenesis in cancer, is associated with diverse cellular processes such as angiogenesis, hypoxia, macrophage polarization, and T-cell activation. This phenomenon is intimately linked with multiple diseases including neoplasia, sepsis, and autoimmune diseases 1,2 . Lactate, a compound generated during Warburg effect, is widely known as an energy source and metabolic byproduct. However, its non-metabolic functions in physiology and disease remain unknown. Here we report lactate-derived histone lysine lactylation as a new epigenetic modification and demonstrate that histone lactylation directly stimulates gene transcription from chromatin. In total, we identify 28 lactylation sites on core histones in human and mouse cells. Hypoxia and bacterial challenges induce production of lactate through glycolysis that in turn serves as precursor for stimulating histone lactylation. Using bacterially exposed M1 macrophages as a model system, we demonstrate that histone lactylation has different temporal dynamics from acetylation. In the late phase of M1 macrophage polarization, elevated histone lactylation induces homeostatic genes involved in wound healing including arginase 1. Collectively, our results suggest the presence of an endogenous “lactate clock” in bacterially challenged M1 macrophages that turns on gene expression to promote homeostasis. Histone lactylation thus represents a new avenue for understanding the functions of lactate and its role in diverse pathophysiological conditions, including infection and cancer.
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              The gut microbiota, bacterial metabolites and colorectal cancer.

              Petra Louis, Georgina L. Hold, Harry J. Flint (2014)
              Accumulating evidence suggests that the human intestinal microbiota contributes to the aetiology of colorectal cancer (CRC), not only via the pro-carcinogenic activities of specific pathogens but also via the influence of the wider microbial community, particularly its metabolome. Recent data have shown that the short-chain fatty acids acetate, propionate and butyrate function in the suppression of inflammation and cancer, whereas other microbial metabolites, such as secondary bile acids, promote carcinogenesis. In this Review, we discuss the relationship between diet, microbial metabolism and CRC and argue that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Microb Cell
                Journal ID (iso-abbrev): Microb Cell
                Journal ID (publisher-id): Microb Cell
                Title: Microbial Cell
                Publisher: Shared Science Publishers OG
                ISSN (Electronic): 2311-2638
                Publication date (Electronic, pub): 08 February 2023
                Publication date (Electronic, collection): 06 March 2023
                Volume: 10
                Issue: 3
                Pages: 49-62
                Affiliations
                [1 ]Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
                [2 ]Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
                [3 ]Department of Infectious Diseases, Shanghai Ruijin Hospital, Shanghai 200025, China.
                [4 ]State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
                [5 ]Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100), Shanghai 200025, China.
                Author notes
                * Corresponding Author: Yu-Feng Yao, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Email: yfyao@ 123456sjtu.edu.cn

                Conflict of Interest: The authors have declared no conflict of interest.

                Please cite this article as: Huang Tang, Wanqiu Huang and Yu-Feng Yao ( 2023). The metabolites of lactic acid bacteria:classification, biosynthesis and modulation of gut microbiota. Microbial Cell 10(3): 49-62. doi: 10.15698/mic2023.03.792

                Article
                Publisher ID: MIC0272E134
                DOI: 10.15698/mic2023.03.792
                PMC ID: 9993431
                PubMed ID: 36908281
                SO-VID: 24143551-634c-4a65-ac27-816dd03895a4
                Copyright © Copyright: © 2023 Tang et al.
                License:

                This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

                History
                Date received : 18 October 2022
                Date revision received : 11 January 2023
                Date accepted : 17 January 2023
                Funding
                This work was supported by grants from the National Natural Science Foundation of China (No. 81830068, No. 81772140, No. 31700120, and No. 81501733), Key Research and Development Project of China (No. 2016YFA0500600), GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine, the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning.
                Categories
                Subject: Review
                Subject: Metabolites
                Subject: Lactic Acid Bacteria
                Subject: Gut Microbiota
                Subject: Immune System

                Keywords: metabolites,lactic acid bacteria,gut microbiota,immune system
                Data availability:
                Keywords: metabolites, lactic acid bacteria, gut microbiota, immune system

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