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      Alteration of the gut fecal microbiome in children living with HIV on antiretroviral therapy in Yaounde, Cameroon

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          Abstract

          Multiple factors, such as immune disruption, prophylactic co-trimoxazole, and antiretroviral therapy, may influence the structure and function of the gut microbiome of children infected with HIV from birth. In order to understand whether HIV infection altered gut microbiome and to relate changes in microbiome structure and function to immune status, virological response and pediatric ART regimens, we characterized the gut microbiome of 87 HIV-infected and 82 non-exposed HIV-negative children from Yaounde, a cosmopolitan city in Cameroon. We found that children living with HIV had significantly lower alpha diversity in their gut microbiome and altered beta diversity that may not be related to CD4+ T cell count or viral load. There was an increased level of Akkermansia and Faecalibacterium genera and decreased level of Escherichia and other Gamma proteobacteria in children infected with HIV, among other differences. We noted an effect of ethnicity/geography on observed gut microbiome composition and that children on ritonavir-boosted protease inhibitor (PI/r)-based ART had gut microbiome composition that diverged more from HIV-negative controls compared to those on non-nucleoside reverse-transcriptase inhibitors-based ART. Further studies investigating the role of this altered gut microbiome in increased disease susceptibility are warranted for individuals who acquired HIV via mother-to-child transmission.

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          Human gut microbiome viewed across age and geography

          Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ between human populations when viewed from the perspective of component microbial lineages, encoded metabolic functions, stage of postnatal development, and environmental exposures, we characterized bacterial species present in fecal samples obtained from 531 individuals representing healthy Amerindians from the Amazonas of Venezuela, residents of rural Malawian communities, and inhabitants of USA metropolitan areas, as well as the gene content of 110 of their microbiomes. This cohort encompassed infants, children, teenagers and adults, parents and offspring, and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the representation of genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial species assemblages and functional gene repertoires were noted between individuals residing in the USA compared to the other two countries. These distinctive features are evident in early infancy as well as adulthood. In addition, the similarity of fecal microbiomes among family members extends across cultures. These findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations, and the impact of Westernization.
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            Introduction to the human gut microbiota

            The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions.
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              Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients.

              A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CD patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-kappaB activity, F. prausnitzii had no effect on IL-1beta-induced NF-kappaB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-gamma production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-kappaB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.
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                Author and article information

                Contributors
                nkenfou@yahoo.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                7 April 2021
                7 April 2021
                2021
                : 11
                : 7666
                Affiliations
                [1 ]GRID grid.29273.3d, ISNI 0000 0001 2288 3199, Department of Medical Laboratory Sciences, Faculty of Health Sciences, , University of Buea, ; Buea, Cameroon
                [2 ]GRID grid.412661.6, ISNI 0000 0001 2173 8504, Medical Microbiology Laboratory, , Yaounde University Teaching Hospital, ; Yaounde, Cameroon
                [3 ]Chantal Biya International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaounde, Cameroon
                [4 ]GRID grid.241116.1, ISNI 0000000107903411, Department of Medicine, School of Medicine, , University of Colorado, ; Denver, USA
                [5 ]GRID grid.428999.7, ISNI 0000 0001 2353 6535, Department of Computational Biology, , Institut Pasteur, USR 3756 CNRS, ; Paris, France
                [6 ]GRID grid.412661.6, ISNI 0000 0001 2173 8504, Department of ETN, Faculty of Medicine and Biomedical Sciences, , University of Yaounde I, ; Yaounde, Cameroon
                [7 ]GRID grid.412661.6, ISNI 0000 0001 2173 8504, Higher Teachers’ Training College, , University of Yaounde I, ; Yaounde, Cameroon
                Article
                87368
                10.1038/s41598-021-87368-8
                8027858
                33828220
                1d194e11-f5bb-4b86-84fc-9ebb767f8653
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 31 August 2020
                : 15 March 2021
                Categories
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                © The Author(s) 2021

                Uncategorized
                microbial communities,microbial genetics
                Uncategorized
                microbial communities, microbial genetics

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