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      Emergence of alternative stable states in microbial communities undergoing horizontal gene transfer

      research-article
      1 , 1 , 1 ,
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      eLife
      eLife Sciences Publications, Ltd
      microbial community, multistability, horizontal gene transfer, plasmid, antiobiotic resistance, microbial diversity, Other

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          Abstract

          Microbial communities living in the same environment often display alternative stable states, each characterized by a unique composition of species. Understanding the origin and determinants of microbiome multistability has broad implications in environments, human health, and microbiome engineering. However, despite its conceptual importance, how multistability emerges in complex communities remains largely unknown. Here, we focused on the role of horizontal gene transfer (HGT), one important aspect mostly overlooked in previous studies, on the stability landscape of microbial populations. Combining mathematical modeling and numerical simulations, we demonstrate that, when mobile genetic elements (MGEs) only affect bacterial growth rates, increasing HGT rate in general promotes multistability of complex microbiota. We further extend our analysis to scenarios where HGT changes interspecies interactions, microbial communities are subjected to strong environmental selections and microbes live in metacommunities consisting of multiple local habitats. We also discuss the role of different mechanisms, including interspecies interaction strength, the growth rate effects of MGEs, MGE epistasis and microbial death rates in shaping the multistability of microbial communities undergoing HGT. These results reveal how different dynamic processes collectively shape community multistability and diversity. Our results provide key insights for the predictive control and engineering of complex microbiota.

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          Most cited references58

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          Enterotypes of the human gut microbiome.

          Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
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            • Article: not found

            Vaginal microbiome of reproductive-age women.

            The means by which vaginal microbiomes help prevent urogenital diseases in women and maintain health are poorly understood. To gain insight into this, the vaginal bacterial communities of 396 asymptomatic North American women who represented four ethnic groups (white, black, Hispanic, and Asian) were sampled and the species composition characterized by pyrosequencing of barcoded 16S rRNA genes. The communities clustered into five groups: four were dominated by Lactobacillus iners, L. crispatus, L. gasseri, or L. jensenii, whereas the fifth had lower proportions of lactic acid bacteria and higher proportions of strictly anaerobic organisms, indicating that a potential key ecological function, the production of lactic acid, seems to be conserved in all communities. The proportions of each community group varied among the four ethnic groups, and these differences were statistically significant [χ(2)(10) = 36.8, P < 0.0001]. Moreover, the vaginal pH of women in different ethnic groups also differed and was higher in Hispanic (pH 5.0 ± 0.59) and black (pH 4.7 ± 1.04) women as compared with Asian (pH 4.4 ± 0.59) and white (pH 4.2 ± 0.3) women. Phylotypes with correlated relative abundances were found in all communities, and these patterns were associated with either high or low Nugent scores, which are used as a factor for the diagnosis of bacterial vaginosis. The inherent differences within and between women in different ethnic groups strongly argues for a more refined definition of the kinds of bacterial communities normally found in healthy women and the need to appreciate differences between individuals so they can be taken into account in risk assessment and disease diagnosis.
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              Gut microbial metabolites in obesity, NAFLD and T2DM

              Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.

                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                03 March 2025
                2025
                : 13
                : RP99593
                Affiliations
                [1 ] Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences ( https://ror.org/04gh4er46) Shenzhen China
                Boston College ( https://ror.org/02n2fzt79) United States
                University of Zurich ( https://ror.org/02crff812) Switzerland
                Boston College ( https://ror.org/02n2fzt79) United States
                Shenzhen Institutes of Advanced Technology Shenzhen China
                Shenzhen Institutes of Advanced Technology Shenzhen China
                Shenzhen Institutes of Advanced Technology Shenzhen China
                Author information
                https://orcid.org/0009-0000-5176-5095
                Article
                99593
                10.7554/eLife.99593
                11875537
                40029705
                8177adbe-3b6a-4c58-80ca-1649054e60e8
                © 2024, Hong et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 18 June 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 12401660
                Award Recipient :
                Funded by: Shenzhen Institue of Synthetic Biology Scientific Research Program;
                Award ID: HSE499011086
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Physics of Living Systems
                Custom metadata
                Mathematical models of horizontal gene transfer reveal the determinants underlying multistability of microbial communities, offering key insights for the predictive control and engineering of complex microbiota.
                prc

                Life sciences
                microbial community,multistability,horizontal gene transfer,plasmid,antiobiotic resistance,microbial diversity,other

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