Activation of probiotic bifidobacteria by milk glyans

Project: Research project

Project Details

Description

Program Director/Principal Investigator (Last, First, Middle): MIIIS, D a v l d , A .
PROJECT SUMMARY (See instmctions):
The use of prebiotics and probiotics to restore a healthy gut microbiota represent a desirable target, but the
lack of mechanistically relevant signatures of how specific bacteria interact with the intestinal environment
and the host has hindered the development of effective and well-characterized prebiotic and probiotic
treatments. The long-term goal is to translate the successful strategy of mammalian lactation, shown using
human milk glycans, to the development of targeted, effective synbiotics by using plentiful and available
bovine milk glycan streams. The overarching hypothesis to be tested is that the evolutionary relationship
between infant-borne bifidobacteria and bovine milk glycans and glycoconjugates produce a synergistic
human milk glycan-like phenotype that can effectively colonize, restore a healthy gut microbiota and induce
host response to better protect epithelial barrier function and thus improve health outcomes. First, the team
will address whether in infant-borne bifidobacteria species, complex milk glycoconjugates induce specific
glycosyl hydrolases and transporters that are necessary to consume these complex substrates. Milk
glycoconjugate catabolism by infant-borne bifidobacteria will be examined by detailed transcriptomics,
specific enzymatic and transporter analysis, and glycoprofiling to identify precise links between glycan
components and their cognate bifidobacterial processing mechanisms. Second, the research team will
determine whether select infant-borne bifidobacteria that consume complex milk glycoconjugates compared
to simple sugar substrates are more effective in inducing a protective response within the host epithelium.
Measurements of bifidobacterial adherence, improved barrier function, release of inflammatory mediators
and activation of enteroendocrine cells will be obtained from gut epithelial and enteroendocrine cells in vitro
and ex vivo in rat small and large intestinal tissue. Finally, the team will determine whether modulation of
intestinal function by application of synbiotic milk glycan- and glycoconjugate-consuming bifidobacteria
improves outcomes in a rodent model of intestinal and metabolic disease. The significance of this project is
that it will take a systematic and mechanistic approach to understanding the synbiotic relationship.
RELEVANCE (See instmctions):
The gut microbiome is a crucial component of human health. Safe and effective approaches for correcting,
maintaining, and guiding establishment of a healthy gut microbiota, particularly in infancy and early
childhood, are needed. The project is relevant to NCCAM's mission because it supports a portfolio of
synbiotic interventions for improving health, with mechanistic signatures of biological effects.
StatusFinished
Effective start/end date9/30/148/30/19

Funding

  • National Institutes of Health: $856,424.00
  • National Institutes of Health: $829,545.00

ASJC

  • Medicine(all)

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