Oligosaccharide cross-feeding and competition in microbial communities

Microbial carbohydrate metabolism is typically assayed by measuring biomass accumulation in pure cultures on a defined carbon source. This approach may obscure what occurs in natural microbial communities where cooperation or competition with other species may exist, where metabolic intermediate are generated that other species may utilize, and it ignores the physical features of the environment where that community resides. Humans host a taxonomically and functionally diverse microbial community in their gastrointestinal tracts that is influenced by multiple intrinsic and extrinsic factors that remain ill-defined. Extrinsic carbohydrate nutrients (diet- or host-derived) can support the growth of microbes that can access and utilize those nutrients. How bacteria intrinsically alter the nutrient landscape of their environment and how/whether active bacterial processes promote competition or cooperation for carbohydrate nutrients remains unclear. We have identified oligosaccharide intermediates produced during dietary plant polysaccharide (fiber) degradation that are structurally modified by bacteria before being released into the environment. We hypothesize that select human gut bacteria generate modified oligosaccharides to create extracellular nutrient reservoirs, enhancing their fitness and that of their kin in competitive environments. Over the next five years, we will first define the structures of modified oligosaccharides produced by gut bacteria to determine how human gut microbes synergize anabolism and catabolism to alter the pool of available carbohydrate nutrients. Next, we will establish how oligosaccharide structures influence the ability of bacteria to acquire, degrade, and utilize nutrients by employing forward- and reverse genetics approaches and synthetic microbial communities. Lastly, we will establish how microbial community composition and host diet shape oligosaccharide nutrient availability along the length of the gastrointestinal tract using mass spectrometry imaging. Using the mammalian gut microbiota as a model microbial community, we will define an intrinsic role for bacteria in shaping carbon nutrient accessibility. Our study will reveal an active biochemical mechanism that bacteria employ in nutrient- competitive environments to obtain carbohydrate nutrients and compete against other species. Project Number: 1R35GM162369-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Darryl Wesener | Institution: OHIO STATE UNIVERSITY, Columbus, OH | Award Amount: $375,898 | Activity Code: R35 | Study Section: Special Emphasis Panel[ZRG1 MGG-F (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11272231