Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan-Dec;15(1):2192151.
doi: 10.1080/19490976.2023.2192151.

Microbial metabolites as modulators of the infant gut microbiome and host-microbial interactions in early life

Henrik M Roager  1 , Catherine Stanton  2 , Lindsay J Hall  3   4   5
Affiliations
Review

Microbial metabolites as modulators of the infant gut microbiome and host-microbial interactions in early life

Henrik M Roager et al. Gut Microbes. 2023 Jan-Dec.

Abstract

The development of infant gut microbiome is a pivotal process affecting the ecology and function of the microbiome, as well as host health. While the establishment of the infant microbiome has been of interest for decades, the focus on gut microbial metabolism and the resulting small molecules (metabolites) has been rather limited. However, technological and computational advances are now enabling researchers to profile the plethora of metabolites in the infant gut, allowing for improved understanding of how gut microbial-derived metabolites drive microbiome community structuring and host-microbial interactions. Here, we review the current knowledge on development of the infant gut microbiota and metabolism within the first year of life, and discuss how these microbial metabolites are key for enhancing our basic understanding of interactions during the early life developmental window.

Keywords: Metabolites; diet; health; host; infants; metabolomics; microbiota.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Gut microbiota-derived metabolites in early life. Gut microbial metabolism changes in early life with the progression in early nutrition from breastfeeding to solid foods concurrent with a progression in microbiome and metabolome diversity. During breastfeeding, the dominance of the infant gut by human milk oligosaccharide (HMO) degrading Bifidobacterium species results in high levels of lactate and acetate, as well as in aromatic lactic acids (i.e. phenyllactic acid, 4-hydroxyphenyllactic acid and indolelactic acid). With the progression in diet, the dietary complexity increases and more indigestible proteins and fiber end up in the colon of the child. Consequently, colonic fermentation changes resulting in the formation of short-chain fatty acids (SCFA, i.e. acetate, propionate and butyrate) and gases (i.e. hydrogen and methane). Furthermore, proteins are degraded into amino acids, which are fermented by the resident gut microbes into branched SCFAs (i.e. isobutyrate, isovalerate and 2-methylbutyrate), amines (i.e. histamine, dopamine, tyramine, γ-aminobutyric acid (GABA), tryptamine), as well as aromatic acetic and propionic acids (e.g. indoleacetic acid and indolepropionic acid).
Figure 2.
Figure 2.
Microbial metabolites as modulators of the infant gut microbial ecosystem. An illustration of the ways in which microbial metabolites are thought to impact the development of the gut microbiome ecosystem during infancy. Human milk oligosaccharides (HMOs) of breast milk are likely to enter the distal gut and be degraded by HMO degraders (for example Bifidobacterium Bacteroides, Ruminococcus and Akkermansia). Among the HMO degraders, particular Bifidobacterium species are important as they are specialized in HMO degradation. Some Bifidobacterium species (mainly B. longum subsp. longum, B. bifidum and B. breve) degrade HMOs extracellular, whereas other Bifidobacterium species (mainly B. longum subsp. infantis) take up the HMOs via ABC transporters and metabolize them inside the cell. The sharing or lack of sharing of nutrients (both carbon sources and micronutrients) have consequences for cross-feeding and competition in the infant gut microbiome affecting the microbial community structure. As the child transitions from a milk-based diet to a solid food-based diet, the microbiome diversity increases and the cross-feeding networks change. Other primary degraders of dietary fibers (typically belonging to Lachnospiracea, Bacteroideacea, Clostridiacea) take over and replace the Bifidobacterium species. Generation of specific microbial metabolites may be key for colonization resistance toward pathobionts when microbiome diversity is low. The pathobionts may be excluded or kept low in abundance through low intestinal pH (due to short-chain fatty acids, SCFAs), through direct antimicrobial activity such as bacteriocins, which are antimicrobial, or simply through nutrient limitations.
Figure 3.
Figure 3.
Dynamics of selected signaling metabolites in the infant gut and their interaction with host receptors. The figure illustrates the change in relative abundances of known key microbiota-derived metabolites generated from saccharolytic and proteolytic fermentation, as well as from bile acid metabolism in the infant gut. The metabolite profiles change as the infant goes from breastfeeding to solid foods concurrent with a maturation of the gut microbiome from a less to a more diverse microbiome. The main host receptor targets for each of the signaling metabolites is indicated to the right. As indicated by the arrows, some metabolites can bind several different host receptors.
Figure 4.
Figure 4.
Gut microbiota-derived metabolites as mediators of host-microbial cross-talk in early life. The microbiota-derived metabolites can impact host development in various ways as they activate different host receptors. For example, microbiota-derived metabolites can stimulate the intestinal immune system (affecting release of cytokines), enteroendocrine cells (affecting release of gut hormones), and enterochromaffin cells (affecting release of serotonin). Subsequently, the secreted molecules can affect the intestinal barrier and immune function, the intestinal nervous system with effects on intestinal motility and the gut-brain axis, and potentially the host metabolism and inflammation throughout the body upon absorption and circulation through the portal vein.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Stewart CJ, Ajami NJ, O’brien JL, Hutchinson DS, Smith DP, Wong MC, Ross MC, Lloyd RE, Doddapaneni H, Metcalf GA, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;562(7728):583–22. doi:10.1038/s41586-018-0617-x. - DOI - PMC - PubMed
    1. Tamburini S, Shen N, Wu HC, Clemente JC.. The microbiome in early life: implications for health outcomes. Nat Med. 2016;22(7):713–722. doi:10.1038/nm.4142. - DOI - PubMed
    1. Dominguez-Bello MG, Godoy-Vitorino F, Knight R, Blaser MJ. Role of the microbiome in human development. Gut. 2019;68:1108–1114. doi:10.1136/gutjnl-2018-317503. - DOI - PMC - PubMed
    1. Ratsika A, Codagnone MC, O’mahony S, Stanton C, Cryan JF. Priming for life: early life nutrition and the microbiota-gut-brain axis. Nutrients. 2021;13:1–33. doi:10.3390/nu13020423. - DOI - PMC - PubMed
    1. Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J, Belzer C, Delgado Palacio S, Arboleya Montes S, Mancabelli L, et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev. 2017;81(4). doi:10.1128/MMBR.00036-17. - DOI - PMC - PubMed

Publication types