Post-birth there is a bacterial assault on all mucosal surfaces. The intestinal microbiome is an important participant in health and disease. The pattern of composition and concentration of the intestinal microbiome varies greatly. Therefore, achieving immunological tolerance in the first 3–4 years of life is critical for maintaining health throughout a lifetime. Probiotic bacteria are organisms that afford beneficial health effects to the host and in certain instances may protect against the development of disease. The potential benefits of modifying the composition of the intestinal microbial cohort for therapeutic benefit is evident in the use in high risks groups such as premature infants, children receiving antibiotics, rotavirus infections in non-vaccinated children and traveler's diarrhea in adults. Probiotics and prebiotics are postulated to have immunomodulating capabilities by influencing the intestinal microbial cohort and dampening the activity of pathobiont intestinal microbes, such as Klebsiella pneumonia and Clostridia perfringens. Lactobacilli and Bifidobacteria are examples of probiotics found in the large intestine and so far, the benefits afforded to probiotics have varied in efficacy. Most likely the efficacy of probiotic bacteria has a multifactorial dependency, namely on a number of factors that include agents used, the dose, the pattern of dosing, and the characteristics of the host and the underlying luminal microbial environment and the activity of bacteriophages. Bacteriophages, are small viruses that infect and lyse intestinal bacteria. As such it can be posited that these viruses display an effective local protective control mechanism for the intestinal barrier against commensal pathobionts that indirectly may assist the host in controlling bacterial concentrations in the gut. A co-operative activity may be envisaged between the intestinal epithelia, mucosal immunity and the activity of bacteriophages to eliminate pathobiots, highlighting the potential role of bacteriophages in assisting with maintaining intestinal homeostasis. Hence bacteriophage local control of inflammation and immune responses may be an additional immunological defense mechanism that exploits bacteriophage–mucin glycoprotein interactions that controls bacterial diversity and abundance in the mucin layers of the gut. Moreover, and importantly the efficacy of probiotics may be dependent on the symbiotic incorporation of prebiotics, and the abundance and diversity of the intestinal microbiome encountered. The virome may be an important factor that determines the efficacy of some probiotic formulations.

The brain and the gut are connected from early fetal life. The mother’s exposure to microbial molecules is thought to exert in utero developmental effects on the fetus. These effects could importantly underpin the groundwork for subsequent pathophysiological mechanisms for achieving immunological tolerance and metabolic equilibrium post birth, events that continue through to 3–4 years of age. Furthermore, it is understood that the microbiome promotes cues that instruct the neonate’s mucosal tissues and skin in the language of molecular and cellular biology. Post birth mucosal lymphoid tissue formation and maturation (most probably including the vermiform appendix) is microbiota-encouraged co-establishing the intestinal microbiome with a developing immune system. Intestinal mucosal tissue maturation loops the brain-gut-brain and is postulated to influence mood dispositions via shifts in the intestinal microbiome phyla. A plausible appreciation is that dysregulated pro-inflammatory signals from intestinal resident macrophages could breach the loop by providing adverse mood signals via vagus nerve afferents to the brain. In this commentary, we further suggest that the intestinal resident macrophages act as an upstream traffic controller of translocated microbes and metabolites in order to maintain local neuro-endocrine-immunological equilibrium. When macrophages are overwhelmed through intestinal microbiome and intestinal epithelial cell dysbiosis, pro-inflammatory signals are sustained, which may then lead to mood disorders. The administration of probiotics as an adjunctive medicine co-administered with antidepressant medications in improving depressed mood may have biological and clinical standing.