Genomic determinants and ecological interactions of human associated akkermansia grown on core human milk oligosaccharides - akkermansia muciniphila is a mucin-degrading bacterium common to the…

The National Institute of Allergy and Infectious Diseases awarded The University Corporation $147,500 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855).

The recipient will conduct research to define the genomic and metabolic determinants by which select Akkermansia species and strains degrade non-fucosylated core human milk oligosaccharides (HMOs) during growth, and to identify ecological interactions among Akkermansia and other HMO-degrading bacteria of the infant gut microbiota. Akkermansia muciniphila is a mucin-degrading bacterium common to the human gut shown to positively impact human health, but the genus is diverse and lacks clear understanding of how this diversity impacts physiological activity and ecological dynamics across the lineage. The research aims to support the long-term goal of developing targeted therapeutic uses of Akkermansia through either stimulating endogenous strains with dietary interventions or administering species as probiotics. The proposed studies will inform strategies to stimulate or administer Akkermansia throughout human life, including in adults through prebiotic dietary formulations.

The University Corporation is a non-profit auxiliary organization of California State University, Northridge, based in Northridge, California. The award covers the period September 1, 2026, through August 31, 2030, with performance in Northridge, CA.

Genomic determinants and ecological interactions of human associated akkermansia grown on core human milk oligosaccharides - akkermansia muciniphila is a mucin-degrading bacterium common to the human GUT that has been shown to positively impact human health. However, the akkermansia genus is diverse, and we lack a clear understanding of how this diversity impacts the physiological activity and ecological dynamics across the lineage. The long- term goal of our research program is to help develop targeted, therapeutic uses of akkermansia, either through stimulating endogenous strains with dietary interventions (~70% prevalence) or by administering species as probiotics in a context-dependent manner. Before these therapeutic applications can be realized, we need a deeper understanding of the metabolic strategies and ecological dynamics that allow each akkermansia species to colonize, compete, and persist in the GUT. The overall objectives for this application are (i) to define the genomic and metabolic determinants by which select akkermansia species and strains degrade non-fucosylated, core human milk oligosaccharides (hmos) during growth, and (II) to identify ecological interactions among akkermansia and other HMO-degrading bacteria of the infant GUT microbiota. The rationale for prioritizing experiments using hmos is that they are selective, dietary substrates known to influence the composition, development, and activity of the GUT microbiota early in life. Further, although hmos are typically available only during breastfeeding, hmos are used in prebiotic dietary formulations for adults. Thus, the proposed studies will inform strategies to stimulate or administer akkermansia throughout human life. The central hypothesis of this application is that the increased genomic capacity for sugar degradation observed in select akkermansia genomes will result in more efficient and potentially novel mechanisms of degradation of non-fucosylated, core hmos by those species/strains. Further, because of the more efficient use of hmos by these species, they will be able to CO-exist with or potentially outcompete other HMO-degrading bacteria. To test these hypotheses, we will use laboratory cultivation studies coupled with multi-omic (i.e., genomic, transcriptomic, and metabolomic) approaches to investigate two independent, but complimentary specific aims: (1) - identify the genomic determinants and metabolic output of growth on the core hmos lacto-n-tetraose (LNT) and lacto-n-neotetraose (lnnt) across (aim 1A) and within (aim 1B) human-associated akkermansia species. (2) characterize the ecological interactions among select akkermansia and bifidobacterium species when CO-cultured on LNT and lnnt. This work is expected to have a significant impact because akkermansia are being pursued for various therapeutic applications with an incomplete understanding of their basic biology. Given that akkermansia species are functionally distinct, identifying mechanisms that favor one species over another in a context-dependent manner may inform future therapeutic interventions specific to a particular disease state or life-stage. Studies will be conducted by student scientists at a primarily undergraduate institution, simultaneously fulfilling the research and training missions of the national institute of general medical sciences.