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Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next-generation drugs, vaccinomics, and metabolic agents and in novel food discovery., (© 2015 American Society for Nutrition.)

Systemic disease caused by transmucosal passage of enterovirulent bacteria and toxins from the gut lumen into the mesenteric lymph nodes (MLN) is reviewed, with particular concern for bacterial interactions in the developing gut of premature newborns. Anaerobic bacteria are rarely observed to translocate to the MLN. Bifidobacterial strains have been tested for their abilities to adhere to enterocyte-like Caco-2 cells in culture. We have investigated the inhibitory effect of adherent human bifidobacterial strains against colonization by a number of diarrheagenic bacteria (Escherichia coli O157; Salmonella typhimurium) and viruses (murine and rhesus rotavirus), in various in vitro and in vivo models. The phagocytic cell (macrophage) may be a key factor in bacterial translocation (BT). Human breast milk contains abundant bioactive substances (immunologic, nutritional) that provide protective effects through inhibition of bacterial overgrowth and BT. New biotherapeutic therapies that stimulate beneficial anaerobic microflora (Lactobacillus, Bifidobacterium) are promising avenues of research to combat BT in disease treatment.