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      The small intestine: dining table of host–microbiota meetings

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          Abstract

          Growing evidence suggests the importance of the small intestinal bacteria in the diet–host–microbiota dialogue in various facets of health and disease. Yet, this body site is still poorly explored and its ecology and mechanisms of interaction with the host are just starting to be unraveled. In this review, we describe the current knowledge on the small intestinal ecology, its composition and diversity, and how the intestinal bacteria in homeostatic conditions participate in nutrient digestion and absorption. We illustrate the importance of a controlled bacterial density and of the preservation of absorptive surface for the host’s nutritional status. In particular, we discuss these aspects of the small intestinal environment in the framework of two disease conditions, namely small intestinal bacterial overgrowth (SIBO) and short bowel syndrome (SBS). We also detail in vivo, ex vivo, and in vitro models developed to simulate the small intestinal environment, some applied for (diet–)host–bacteria interaction studies. Lastly, we highlight recent technological, medical, and scientific advances applicable to investigate this complex and yet understudied body environment to broaden our knowledge in support of further progress in the medical practice, and to proceed towards the integration of the (small)intestinal bacteria in personalized therapeutic approaches.

          Abstract

          Updated overview on the interaction between diet, host and microbiota in the small intestine of adult humans, in healthy and disease conditions.

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          Most cited references335

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          Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences

          Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for studies of microbial communities but does not provide direct evidence of a community’s functional capabilities. Here we describe PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a computational approach to predict the functional composition of a metagenome using marker gene data and a database of reference genomes. PICRUSt uses an extended ancestral-state reconstruction algorithm to predict which gene families are present and then combines gene families to estimate the composite metagenome. Using 16S information, PICRUSt recaptures key findings from the Human Microbiome Project and accurately predicts the abundance of gene families in host-associated and environmental communities, with quantifiable uncertainty. Our results demonstrate that phylogeny and function are sufficiently linked that this ‘predictive metagenomic’ approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.
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            Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium.

            We previously established long-term culture conditions under which single crypts or stem cells derived from mouse small intestine expand over long periods. The expanding crypts undergo multiple crypt fission events, simultaneously generating villus-like epithelial domains that contain all differentiated types of cells. We have adapted the culture conditions to grow similar epithelial organoids from mouse colon and human small intestine and colon. Based on the mouse small intestinal culture system, we optimized the mouse and human colon culture systems. Addition of Wnt3A to the combination of growth factors applied to mouse colon crypts allowed them to expand indefinitely. Addition of nicotinamide, along with a small molecule inhibitor of Alk and an inhibitor of p38, were required for long-term culture of human small intestine and colon tissues. The culture system also allowed growth of mouse Apc-deficient adenomas, human colorectal cancer cells, and human metaplastic epithelia from regions of Barrett's esophagus. We developed a technology that can be used to study infected, inflammatory, or neoplastic tissues from the human gastrointestinal tract. These tools might have applications in regenerative biology through ex vivo expansion of the intestinal epithelia. Studies of these cultures indicate that there is no inherent restriction in the replicative potential of adult stem cells (or a Hayflick limit) ex vivo. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              Identification of stem cells in small intestine and colon by marker gene Lgr5.

              The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the +4 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. Here, using two knock-in alleles, we reveal exclusive expression of Lgr5 in cycling columnar cells at the crypt base. In addition, Lgr5 was expressed in rare cells in several other tissues. Using an inducible Cre knock-in allele and the Rosa26-lacZ reporter strain, lineage-tracing experiments were performed in adult mice. The Lgr5-positive crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers.
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                Author and article information

                Contributors
                Journal
                FEMS Microbiol Rev
                FEMS Microbiol Rev
                femsre
                FEMS Microbiology Reviews
                Oxford University Press
                0168-6445
                1574-6976
                May 2023
                16 May 2023
                16 May 2023
                : 47
                : 3
                : fuad022
                Affiliations
                Center for Microbial Ecology and Technology (CMET), Department of Biotechnology, Ghent University , Coupure Links 653, Building A, 9000 Ghent, Belgium
                Center for Microbial Ecology and Technology (CMET), Department of Biotechnology, Ghent University , Coupure Links 653, Building A, 9000 Ghent, Belgium
                Université Clermont Auvergne, UMR 454 MEDIS UCA-INRAE , Place Henri Dunant 28, F-63000 Clermont-Ferrand, France
                Université Clermont Auvergne, UMR 454 MEDIS UCA-INRAE , Place Henri Dunant 28, F-63000 Clermont-Ferrand, France
                Center for Microbial Ecology and Technology (CMET), Department of Biotechnology, Ghent University , Coupure Links 653, Building A, 9000 Ghent, Belgium
                Université Clermont Auvergne, UMR 454 MEDIS UCA-INRAE , Place Henri Dunant 28, F-63000 Clermont-Ferrand, France
                Center for Microbial Ecology and Technology (CMET), Department of Biotechnology, Ghent University , Coupure Links 653, Building A, 9000 Ghent, Belgium
                Author notes
                Corresponding author. Center for Microbial Ecology and Technology (CMET), Department of Biotechnology, Ghent University, Coupure Links 653, Building A, 9000 Ghent, Belgium. E-mail: ludovica.marinelli@ 123456ugent.be

                These authors contributed equally.

                Author information
                https://orcid.org/0000-0002-2995-5105
                Article
                fuad022
                10.1093/femsre/fuad022
                10246847
                37193669
                a166c4cc-fb0b-43dd-bcb9-fa18b77dd144
                © The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 October 2022
                : 04 May 2023
                : 14 May 2023
                : 07 June 2023
                Page count
                Pages: 32
                Funding
                Funded by: Ghent University, DOI 10.13039/501100004385;
                Award ID: BOFGOA2022000803
                Categories
                Review Article
                AcademicSubjects/SCI01150

                Microbiology & Virology
                small intestine,microbiota,nutrition,host-bacteria interaction
                Microbiology & Virology
                small intestine, microbiota, nutrition, host-bacteria interaction

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