Objective:In this review,to illustrate the resistance mechanism for pathogen insult,we discussed the role of the intestinal microbiome in promoting resistance to local gastrointestinal tract infections and to respiratory tract infections.Data Sources:The review was based on data obtained from the published research articles.Study Selection:A total of 49 original articles were selected in accordance with our main objective to illustrate the resistance mechanism(s) by which commensal microbiota can contribute to host defense against local and systemic infections.Results:Diverse microorganisms colonize human environmentally exposed surfaces such as skin,respiratory tract,and gastrointestinal tract.Co-evolution has resulted in these microbes with extensive and diverse impacts on multiple aspects of host biological functions.During the last decade,high-throughput sequencing technology developed has been applied to study commensal microbiota and their impact on host biological functions.By using pathogen recognition receptors pathway and nucleotide binding oligomerization domain-like receptors pathway,the commensal microbiome promotes resistance to local and systemic infections,respectively.To protect against the local infections,the microbiome functions contain the following:the competing for sites of colonization,direct production of inhibition molecules or depletion of nutrients needed for pathogens,and priming immune defenses against pathogen insult.At the same time,with the purpose to maintain homeostasis,the commensal bacteria can program systemic signals toward not only local tissue but also distal tissue to modify their function for infections accordingly.Conclusions:Commensal bacteria play an essential role in protecting against infections,shaping and regulating immune responses,and maintaining host immune homeostasis.