Abstract
Background: Over the past decade, there has been recognition of the importance of the human microbiome. Beyond improved microbial cataloguing through high- throughput genetic sequencing, we have learned that human beings are superorganisms integrating the identity, function and immunity of resident bacterial, while prepared throughout own innate and adaptive immune systems, to deal with invading organisms. Hypothesis: In keeping with the dynamic relation of infection, immunity and inflammation contained in I-Cubed, illness arises when protective immunity becomes the source of autoimmunity, conditioned by environmental and genetic factors. Results: This paradigm explains the etiopathogenesis of diverse medical (type 1 diabetes, spondyloarthropathy), neurologic (Lyme neuroborreliosis), and neuropsychiatric disorders (PANDAS, and autism spectrum disorders). Conclusion: Successful treatments employing immune-modulatory therapy may be employed. Public health officials will be called upon to guide the public’s understanding and mitigate the risk of disorders that result from the interplay of the human microbiome and I-Cubed.

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