The human gastrointestinal tract (GIT) microbiome is a key modulator of human health, metabolism, and immune function. Although the large intestine microbiome has been extensively studied in vivo, more detailed characterization of microbiome dynamics, as well as study of the small intestine microbiome which is relatively inaccessible, necessitate use of in vitro models. Here, we present recent progress on GI-jA2COB, an in vitro fermentation model of the combined lower gastrointestinal tract. Use of an automated, parallel bioreactor platform enabled real-time monitoring and control of fermentation parameters including pH, anaerobicity, and volume. Bioreactors representing the ileum and three domains of the colon were cultured either separately under batch conditions for 24-48 hours or in sequence for up to five weeks. Large intestine incoula were prepared from fresh fecal donations pooled from multiple individuals and grown anaerobically. To model the small intestine microbiome, a polymicrobial community representing major small intestine phyla and functions was cultured in a microaerophilic environment representative of the ileum; small intestine nutrient absorption was simulated via filtration. Long-term validation of the sequential lower GIT microbiome model was recently completed and initial results will be discussed. Recent findings utilizing the large intestine batch model with supplementation by a polyphenol, cranberry proanthocyanidin, under different colonic domain conditions indicated a domain-dependent effect on microbial metabolism (results will be presented); a related study employing the sequential lower GIT microbiome model is planned. Use of in vitro fermentation to model the human intestinal microbiota will enable broader investigation of the effect of Soldier-relevant stressors on gut health and may act as a precursor to human or animal studies. Insight gleaned from these models, alone or in concert with in vivo studies, can inform nutritional strategies to restore and maintain Soldier gut homeostasis.

Jason Soares

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