The microbiome as a major function of the gastrointestinal tract and its implication in micronutrient metabolism and chronic diseases.

The composition and function of microbes harbored in the human gastrointestinal lumen have been underestimated for centuries because of the underdevelopment of nucleotide sequencing techniques and the lack of humanized gnotobiotic models. Now, we appreciate that the gut microbiome is an integral part of the human body and exerts considerable roles in host health and diseases. Dietary factors can induce changes in the microbial community composition, metabolism, and function, thereby altering the host immune response, and consequently, may influence disease risks. An imbalance of gut microbiome homeostasis (i.e., dysbiosis) has been linked to several chronic diseases, such as inflammatory bowel diseases, obesity, and diabetes. Remarkable progress has recently been made in better understanding the extent to which the influence of the diet-microbiota interaction on host health outcomes in both animal models and human participants. However, the exact causality of the gut microbiome on the development of diseases is still controversial. In this review, we will briefly describe the general structure and function of the intestine and the process of nutrient absorption in humans. This is followed by a summarization of the recent updates on interactions between gut microbiota and individual micronutrients, including carotenoids, vitamin A, vitamin D, vitamin C, folate, iron, and zinc. In the opinion of the authors, these nutrients were identified as representative of vitamins and minerals with sufficient research on their roles in the microbiome. The host responses to the gut microbiome will also be discussed. Future direction in microbiome research, for example, precision microbiome, will be proposed.

Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes.

Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e., chassis) have difficulty in colonizing the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli bacteria isolated from the stool cultures of CR mice were modified to express functional genes. The reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E. coli can induce functional changes that affect physiology of and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to "knock in" specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts and enables LBT with curative intent.

Precision Microbiome Modulation with Discrete Dietary Fiber Structures Directs Short-Chain Fatty Acid Production.

Dietary fibers (DFs) impact the gut microbiome in ways often considered beneficial. However, it is unknown if precise and predictable manipulations of the gut microbiota, and especially its metabolic activity, can be achieved through DFs with discrete chemical structures. Using a dose-response trial with three type-IV resistant starches (RS4s) in healthy humans, we found that crystalline and phosphate cross-linked starch structures induce divergent and highly specific effects on microbiome composition that are linked to directed shifts in the output of either propionate or butyrate. The dominant RS4-induced effects were remarkably consistent within treatment groups, dose-dependent plateauing at 35 g/day, and can be explained by substrate-specific binding and utilization of the RS4s by bacterial taxa with different pathways for starch metabolism. Overall, these findings support the potential of using discrete DF structures to achieve targeted manipulations of the gut microbiome and its metabolic functions relevant to health.

Microbiome precision editing: Using PEG as a selective fermentation initiator against methicillin-resistant Staphylococcus aureus.

Recent creation of a Unified Microbiome Initiative (UMI) has the aim of understanding how microbes interact with each other and with us. When pathogenic Staphylococcus aureus infects the skin, the interplay between S. aureus and skin commensal bacteria occurs. Our previous data revealed that skin commensal bacteria can mediate fermentation against the growth of USA300, a community-acquired methicillin-resistant S. aureus MRSA. By using a fermentation process with solid media on a small scale, we define poly(ethylene glycol) dimethacrylate (PEG-DMA) as a selective fermentation initiator which can specifically intensify the probiotic ability of skin commensal Staphylococcus epidermidis bacteria. At least five short-chain fatty acids including acetic, butyric and propionic acids with anti-USA300 activities are produced by PEG-DMA fermentation of S. epidermidis. Furthermore, the S. epidermidis-laden PEG-DMA hydrogels effectively decolonized USA300 in skin wounds in mice. The PEG-DMA and its derivatives may become novel biomaterials to specifically tailor the human skin microbiome against invading pathogens.