Fspring is diminished [162]. In 1986, Linda Actidione site Hegstrand and colleague R. Jean Hine

Fspring is diminished [162]. In 1986, Linda Actidione site Hegstrand and colleague R. Jean Hine reported a remarkable discovery to the scientific community–compared to germ-free animals, conventionally raised animals have higher levels of histamine in the hypothalamus [163]. While best known for its connection to allergy, brain histamine in general, and hypothalamic histamine in particular, is a key factor in arousal and behavior [164]. Perhaps underappreciated at the time, their work was a milestone in the gut microbiota-to-brain axis. Although the hygiene hypothesis itself remained focused in the realm of allergy, it was proposed in 2002 that the ways in which beneficial bacteria influence Thelper cells (TH1:TH2 balance) in allergies might also extend to conditions where neurocognitive symptoms are common. When this seemingly outlandish proposal was made (accepted Aug, 2002), it was pointed out that allergies are a frequent overlap with chronic conditions in which emotional and somatic symptoms are a central feature. If TH1:TH2 imbalance was a driver of many emotional and somatic symptoms, then a mitigating role for beneficial microbes was theoretically possible [89]. As the traditional focus on harmful microbes began to shift toward lactic acid bacterium and commensals, novel scientific frameworks began to bridge the immune/nervous systems to neuropsychiatric health via non-pathogenic microbes and nutrition. Although in the early 2000s, these discussions were forced to the fringes, far removed from the safety net of the impending microbiome frenzy, Dubos was not overlooked in the reference lists [89,165]. Over the last decade, experimental and preliminary clinical studies have produced findings that would have been virtually inconceivable to most at the end of the 20th century. Strangely, Dubos has an appallingly low number of citations (to what should have been milestone papers–e.g., [162]) on Google Scholar. Concerning his own groundbreaking studies PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27607577 on the microbiota of the total environment and what it might mean to human well-being, Dubos referred to himself as simply walking in Metchnikoff’s footsteps [166]. Within his book Man Adapting (Yale University Press, 1965), he details his own experiments on fecal microbiota transplantation and immunity. He found that a more sanitized environment reduced intestinal microbial diversity in mice. In this remarkable text, he makes it clear thatLogan et al. Journal of Physiological Anthropology (2015) 34:Page 8 ofpseudo-medico social media [177,178] and overhyping of research by academics [179], his concerns may be particularly relevant. Notwithstanding translation difficulties, the emerging rodent studies have provided some undeniably valuable clues to possible mechanistic pathways between microbes and brain function. Collectively, the experimental studies indicate that beneficial microbes might influence neurocognitive function, behavior, and perceived stress by various pathways: direct communication to the central nervous system (most likely via the vagus nerve), controlling the intestinal barrier (and limiting systemic low-grade inflammation), improvement of nutritional status (phytochemical absorption and neurotransmitter precursors), reducing systemic oxidative stress, regulation of glucose control, and limitation of uremic toxin production [180-183]. Undoubtedly, others will be revealed. In the clinical setting, several studies have shown that oral probiotics, or fermented foods/beverages inclusiv.