Multi-omic investigations into environmental effects on health and disease are aided by inclusion of microbial microbiomes with assessment of mirobes producing metabolites that differentially modulate host organ functions. The gut microbiome is key because many environmental toxicants enter the body orally and may disrupt gut microbes that help digest food, as well as the microbiome-gut-brain axis, which produces regulatory metabolites with systemic effects. Environmental stressors may differentially alter brain development and function, even among identical twins, in that over time, there may be divergence due to epigenetic effects from the environment, including microbes within the microbiome. The diversity of microbiomes is presented as playing a key role in the influence of organs on each other, health, and the development of disorders. The gut microbes and their metabolites may cause mitochondria to produce less ATP and more reactive oxygen species (ROS). The metabolites produced by microbes during the digestion of foods can nourish or harm a person's cellular and molecular functions and vary depending on each person's exposome. The detrimental effects of environmental stressors are discussed, focusing on how altered levels of neuropeptides, neurotransmitters, and the inflammatory/anti-inflammatory balance affect health and disorders. During ATP production, dysfunctional mitochondria may produce more ROS, which can lead to inflammation and oxidative stress, causing cell damage and disrupting products needed for neuronal development, connections, and functions. The balance between inflammatory/anti-inflammatory biomarkers and metabolites and between oxidants/antioxidants is discussed in relation to some clinical connections; for example, the proportions of CD4 and CD8 T cells in HIV patients and the ROS-to-glutathione ratio in inflammatory bowel disease and septic patients. These imbalances are reviewed regarding brain development and functions leading to anxiety, depression, and dementia. The integration of multi-omics, dysbiosis, and mitochondrial dysfunction with a person's clinical evaluation is discussed to inform the formulation of prevention measures and therapeutic interventions regarding environmental effects on the microbiome-gut-brain axis and physical and mental health.
