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      Intestinal Microbiota Dysbiosis Promotes Mucosal Barrier Damage and Immune Injury in HIV-Infected Patients

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          Abstract

          The intestinal microbiota is an “invisible organ” in the human body, with diverse components and complex interactions. Homeostasis of the intestinal microbiota plays a pivotal role in maintaining the normal physiological process and regulating immune homeostasis. By reviewing more than one hundred related studies concerning HIV infection and intestinal microbiota from 2011 to 2023, we found that human immunodeficiency virus (HIV) infection can induce intestinal microbiota dysbiosis, which not only worsens clinical symptoms but also promotes the occurrence of post-sequelae symptoms and comorbidities. In the early stage of HIV infection, the intestinal mucosal barrier is damaged and a persistent inflammatory response is induced. Mucosal barrier damage and immune injury play a pivotal role in promoting the post-sequelae symptoms caused by HIV infection. This review summarizes the relationship between dysbiosis of the intestinal microbiota and mucosal barrier damage during HIV infection and discusses the potential mechanisms of intestinal barrier damage induced by intestinal microbiota dysbiosis and inflammation. Exploring these molecular mechanisms might provide new ideas to improve the efficacy of HIV treatment and reduce the incidence of post-sequelae symptoms.

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          Neuroinflammation in Alzheimer's disease.

          Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.
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            Inflammation and Cancer: Triggers, Mechanisms, and Consequences

            Inflammation predisposes to the development of cancer and promotes all stages of tumorigenesis. Cancer cells as well as surrounding stromal and inflammatory cells engage in well-orchestrated reciprocal interactions to form an inflammatory tumor microenvironment (TME). Cells within the TME are highly plastic, continuously changing their phenotypic and functional characteristics. Here we review the origins of inflammation in tumors, and the mechanisms whereby inflammation drives tumor initiation, growth, progression and metastasis. We discuss how tumor promoting inflammation closely resembles inflammatory processes typically found during development, immunity, maintenance of tissue homeostasis or tissue repair, and illuminate the distinctions between tissue-protective and pro-tumorigenic inflammation, including spatio-temporal considerations. Defining the cornerstone rules of engagement governing molecular and cellular mechanisms of tumor-promoting inflammation will be essential for the further development of anti-cancer therapies. Grivennikov and Greten review the mechanisms underlying the initiation of pro-tumorigenic inflammatory responses, how these evolve throughout the different stages of tumor development and the plasticity of the cells within the tumor microenvironment.
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              Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases

              Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.
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                Author and article information

                Contributors
                Journal
                Can J Infect Dis Med Microbiol
                Can J Infect Dis Med Microbiol
                CJIDMM
                The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale
                Hindawi
                1712-9532
                1918-1493
                2023
                28 October 2023
                : 2023
                : 3080969
                Affiliations
                1Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China
                2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
                Author notes

                Academic Editor: Tingtao Chen

                Author information
                https://orcid.org/0000-0001-9937-2645
                https://orcid.org/0000-0001-5119-3058
                https://orcid.org/0000-0001-6329-1739
                Article
                10.1155/2023/3080969
                10625490
                37927531
                8c3092a8-2cb0-4836-b990-ddc1e3afe434
                Copyright © 2023 Zhaoyi Pan et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 May 2023
                : 8 September 2023
                : 12 October 2023
                Funding
                Funded by: National Basic Research Program of China (973 Program)
                Award ID: 2021YFF0700305
                Funded by: Natural Science Foundation of Shandong Province
                Award ID: SYS202202
                Funded by: Research Project of Jinan Microecological Biomedicine Shandong Laboratory
                Award ID: JNL-2022038C
                Award ID: JNL-2023014D
                Categories
                Review Article

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