Gut Microbiota: Small Molecules Modulate Host Cellular Functions

Luber, Jacob M.; Kostic, Aleksandar D.

doi:10.1016/j.cub.2017.03.026

Cited by 4 publications

(5 citation statements)

References 17 publications

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“…Under homeostatic conditions, the gut microbiota metabolizes the diet- and host-derived substrates available in the intestinal environment, producing a multitude of bioactive metabolites, such as small molecules, with positive impacts on host physiology ( Luber and Kostic, 2017 ). However, developmental adjustments in microbial activities related to the small molecule metabolism in correlation with age remain poorly investigated.…”

Section: Discussionmentioning

confidence: 99%

“…These microbial metabolites can originate both from modifications to host-derived molecules, resulting in the production of branched- and short-chain fatty acids, secondary bile acids, and amino acids derivates such as tryptophan metabolites ( Dai et al, 2011 ; Ridlon et al, 2014 , 2016 ; Morrison and Preston, 2016 ; Liu and Dai, 2020 ), or from de novo synthesis through secondary microbial metabolism (also known as specialized metabolism), which produce a wide range of molecules such as polyketides, non-ribosomal peptides (NRPs), terpenes, NRP synthetase–independent siderophores, and saccharides ( Donia and Fischbach, 2015 ; Postler and Ghosh, 2017 ). Accordingly, a large assortment of small molecules has been isolated from human gut-associated bacteria, highlighting their close involvement in host cellular functions and disease ( Luber and Kostic, 2017 ; Bekkers et al, 2021 ; Tarracchini et al, 2021a ). However, the small molecule repertoire from the human gut microbiota and its evolution from infancy to adulthood have been poorly explored.…”

Section: Introductionmentioning

confidence: 99%

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Gut microbe metabolism of small molecules supports human development across the early stages of life

et al. 2022

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From birth to adulthood, the human gut-associated microbial communities experience profound changes in their structure. However, while the taxonomical composition has been extensively explored, temporal shifts in the microbial metabolic functionalities related to the metabolism of bioactive small molecules are still largely unexplored. Here, we collected a total of 6,617 publicly available human fecal shotgun metagenomes and 42 metatranscriptomes from infants and adults to explore the dynamic changes of the microbial-derived small molecule metabolisms according to the age-related development of the human gut microbiome. Moreover, by selecting metagenomic data from 250 breastfed and 217 formula-fed infants, we also investigated how feeding types can shape the metabolic functionality of the incipient gut microbiome. From the small molecule metabolism perspective, our findings suggested that the human gut microbial communities are genetically equipped and prepared to metabolically evolve toward the adult state as early as 1 month after birth, although at the age of 4 years, it still appeared functionally underdeveloped compared to adults. Furthermore, in respect of formula-fed newborns, breastfed infants showed enrichment in microbial metabolic functions related to specific amino acids present at low concentrations in human milk, highlighting that the infant gut microbiome has specifically evolved to synthesize bioactive molecules that can complement the human breast milk composition contributing to complete nutritional supply of infant.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gut microbe metabolism of small molecules supports human development across the early stages of life

et al. 2022

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“…Host microbiome environments house an enormous range of bacteria that have adapted and thrived in the host’s environment. In the past few years, studies have focused on natural product discovery in the human microbiome and have provided new insight into the search for novel SMs in different environments [15,58]. Another notable example includes the microbiome in marine sponges.…”

Section: Bgc and Natural Product Mining In Different Environmentsmentioning

confidence: 99%

New Approaches to Detect Biosynthetic Gene Clusters in the Environment

2019

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Microorganisms in the environment can produce a diverse range of secondary metabolites (SM), which are also known as natural products. Bioactive SMs have been crucial in the development of antibiotics and can also act as useful compounds in the biotechnology industry. These natural products are encoded by an extensive range of biosynthetic gene clusters (BGCs). The developments in omics technologies and bioinformatic tools are contributing to a paradigm shift from traditional culturing and screening methods to bioinformatic tools and genomics to uncover BGCs that were previously unknown or transcriptionally silent. Natural product discovery using bioinformatics and omics workflow in the environment has demonstrated an extensive distribution of BGCs in various environments, such as soil, aquatic ecosystems and host microbiome environments. Computational tools provide a feasible and culture-independent route to find new secondary metabolites where traditional approaches cannot. This review will highlight some of the advances in the approaches, primarily bioinformatic, in identifying new BGCs, especially in environments where microorganisms are rarely cultured. This has allowed us to tap into the huge potential of microbial dark matter.

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“…Both human gut and microbiota generate abundance of proteins and metabolites which influence the host's physiology and behavior, participate in cancer development and regulate various metabolic pathways . These biomolecules include antibiotics, enzymes, vitamins, amino acids, minerals, energy metabolites, short chain fatty acids (SCFAs), neurotransmitters, hormones, microbial antigens, pathogen‐associated molecular patterns (PAMPs), and toxins, which are “connected” to various organs namely lungs, brain, liver, and muscle via host's circulation . Studies have prevailed on the capability of the host to modulate gut microbial community, for instance, by producing α‐defensins, an antimicrobial peptide responsible to eliminate pathogens and maintain gut homeostasis .…”

Section: The Secretome Studies Of Colorectal Cancermentioning

confidence: 99%

Analyzing the Secretome of Gut Microbiota as the Next Strategy For Early Detection of Colorectal Cancer

et al. 2019

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Dysbiosis of gut microbiome can contribute to inflammation, and subsequently initiation and progression of colorectal cancer (CRC). Throughout these stages, various proteins and metabolites are secreted to the external environment by microorganisms or the hosts themselves. Studying these proteins may help enhance our understanding of the host–microorganism relationship or they may even serve as useful biomarkers for CRC. However, secretomic studies of gut microbiome of CRC patients, until now, are scarcely performed. In this review article, the focus is on the roles of gut microbiome in CRC, the current findings on CRC secretome are highlighted, and the emerging challenges and strategies to drive forward this area of research are addressed.

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Gut Microbiota: Small Molecules Modulate Host Cellular Functions

Cited by 4 publications

References 17 publications

Gut microbe metabolism of small molecules supports human development across the early stages of life

Gut microbe metabolism of small molecules supports human development across the early stages of life

New Approaches to Detect Biosynthetic Gene Clusters in the Environment

Analyzing the Secretome of Gut Microbiota as the Next Strategy For Early Detection of Colorectal Cancer

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