Numerous studies have demonstrated that the gut of healthy adults typically houses an impressive diversity of bacteria, comprising over 1000 distinct species. These bacteria are instrumental in maintaining human health or potentially contributing to the development of diseases. To comprehensively investigate the intricate interactions between gut microbes and the human body, as well as enhance the provision of host-specific nutrients or metabolites by gut bacteria, the utilization of genetic manipulation tools is indispensable.
One exciting avenue with significant potential for improving human health involves the use of genetically engineered bacteria. By strategically designing these bacteria, drawing inspiration from model organisms like E. coli, researchers can harness their capabilities to express beneficial metabolites such as vitamins, short-chain fatty acids, and enzymes. This expression of advantageous compounds not only serves to supplement nutrient intake but also enhances the absorption of nutrients within the host. Notably, engineered E. coli has already exhibited remarkable promise in treating bacterial infections, ulcerative colitis, and phenylketonuria.
Nonetheless, the achievement of genetic manipulation for non-model strains poses a considerable challenge. This endeavor necessitates the identification of suitable genetic markers and plasmid expression vectors, followed by the introduction of candidate plasmids into the recipient bacteria. Subsequently, a range of methods, including gene editing tools like CRISPR-Cas or gene integration systems such as transposon systems, must be employed to facilitate the deletion or modification of specific genes within the bacterial strain or the introduction of novel genes, ultimately yielding recombinant engineered strains.
Furthermore, to unravel the intricate mechanisms underlying host-bacteria interactions, transplantation experiments involving germ-free mice and genetically engineered bacteria are crucial. Germ-free mice, devoid of their native microbiota, provide an ideal model for studying the impact of specific bacterial strains on host physiology. By comparing the effects of wild-type bacteria with those of engineered strains in these germ-free mice, researchers can establish causal relationships between genetic modifications and observed health outcomes, thereby shedding light on the precise mechanisms through which genetically engineered bacteria influence the health and well-being of their hosts.
