While the skin, mouth, nasal cavity, vagina, and urinary tract have benecial, harm­less (commensal), and harmful (pathogenic) microbes (Baquero et al., 2021; Sender et al., 2016; Walsh & Collyns, 2020), most of the research on the inuence of micro­biota on the brain involves gut microbiota. erefore, this chapter will cover the gut microbiome specically. Benet or harm from microbes depends on the complex issue of balance between microbes, the environment, and the host. We may benet by having our immune systems activated in response to a threat (Y. J. Chen et al., 2021; Wang & Kasper, 2014), by the creation of neurotransmitters (Y. J. Chen et al.,

2021), and by regulating our metabolisms (Hemarajata & Versalovic, 2013). e potential harms from microbes include a variety of infections and their sequelae, including cognitive eects (Chakrabarti et al., 2022; Y. J. Chen et al., 2021; Kendig et al., 2021).

the brain regarding stress and anxiety (and involving adrenaline and noradrenaline (norepinephrine)). us, the term “gut– brain axis,” rst used by Track (1983), began to grow in popularity (Lu & Claud, 2019; Miller, 2018).

In 2007, the National Institutes of Health Common Fund of the United States government funded the Human Microbiome Project, which aimed to recruit 300 healthy 18- to 40- year- olds for microbiome analysis (e Human Microbiome Project Consortium, 2012). One nding from this research was that healthy adult participants did not vary in their microbiomes over time as much as one participant varied from another in their microbiomes. ese ndings were based on the 131 participants who provided a second set of samples months later (mean = 219 days, standard deviation = 69 days between the rst and second samples; Aagaard et al., 2013; e Human Microbiome Project Consortium, 2012). However, these ndings do not address changes in the microbiome over the lifespan or in response to var­ious disease states. Detecting dierences between the microbiota of healthy and un­healthy participants was, in fact, one of the motivations for the Human Microbiome Project (Aagaard et al., 2013). More recent studies have indicated that a variety of events states, including mental health conditions, are associated with gut microbiota (Green et al., 2019; Kang et al., 2017; Yan et al., 2021). In addition, it is important to understand what patterns are normal and healthy over the lifespan.

gut microbiota containing their mother’s skin microbiota (Staphylococcus species (spp.)1, Corynebacterium spp., and Propionibacterium spp.), whereas infants born vaginally predominately have their mother’s vaginal bacteria: Lactobacillus spp., Prevotella spp., and Sneathia spp. (Dominguez- Bello et al., 2010). ese dierences have caused some concern about possible health and mental health conditions, in­cluding increased rates of asthma, autism, celiac disease, and insulin- dependent di­abetes mellitus in infants born by cesarean section (Kalliomäki et al., 2001; Q. R. Li et al., 2017; Matamoros et al., 2013; Rautava et al., 2012).

Changes in gut microbiota inuence (and are inuenced by) neuropsychiatric disorders, including those emerging in adolescence. For example, murine models show that gut microbiota inuences mood- like disorders and social anxiety- like dis­orders that typically appear during adolescence (Codagnone et al., 2019; Liang et al., 2018; Robertson et al., 2017). Early postnatal stress, including maternal separation, alters gut microbiota and causes inammation, impairs memory and learning, and increases stress reactivity, including hormonal signs (adrenocorticotropic and cor­ticosterone). At the same time, a high- fat diet early in life (which disrupts gut mi­crobiota) increases binge eating during adolescence and increases stress reactivity (Codagnone et al., 2019). Alternatively, anxiety improved in several studies using a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (Yan et al., 2021).

microbiota and mental health conditions, I discuss ASD, ADHD, schizophrenia, de­pression, Parkinson’s disease, and Alzheimer’s disease.

cognition in schizophrenia. One possible mechanism, identied by several re­searchers (Dash et al., 2022; Tsamakis et al., 2022) suggests that E. coli and Bacteroides fragilis overgrowth leads to inammation which, in turn, may lead to cognitive im­pairment. More specically, Miller et al. (2021) mention Salmonella and E. coli as being associated with both interleukin- 6 (produced in response to infections) and impaired cognition. eir report is based on a 1966 birth cohort from Finland, in which 82 subjects with schizophrenia were compared to controls. Increased blood interleukin- 6 predicted reduced hippocampal volume in schizophrenics (although not reduced cognitive performance at age 32 years).

with the fact that these bacteria are involved in Alzheimer’s disease pathology, mice recolonized with human Alzheimer’s disease fecal samples demonstrated cognitive decits in the maze task.

Generally speaking, changes in gut microbiota inuence neuropsychiatric dis­orders (Codagnone et al., 2019; Liang et al., 2018; Robertson et al., 2017). e gut

microbiota inuences the central nervous system in a variety of ways that might im­pact cognitive function (e.g., aerent nerves, hormones, the immune system, and metabolites, including neurotransmitters). Below, I review evidence for various pos­sible pathways for the mutual inuence of the gut and brain on each other. I have included results of animal studies since they represent initial evidence for a similar process occurring in humans, but we should be extra cautious when applying their ndings to human cognition (Khorshidi et al., 2021). erefore, I emphasize human studies whenever possible.

ere are hundreds of millions of neurons within the wall of the gut that form the enteric nervous system (Anglin et al., 2015). Approximately the rst two- thirds of the gut lumen is in direct contact with the vagus nerve (Heiss & Olofsson, 2019) and can inuence the limbic system and thereby arousal, fear, anxiety, and emotion reg­ulation (Anglin et al., 2015). While kissing and caring for infants likely have psycho­logical benets beyond a method for transferring microbes, it is interesting to think of the benets from the microbe’s perspective. e positioning of the birth canal so close to the anus usually ensures the transmission of microbes from both the vagina and gut. Infants cannot help but be inhabited by microbes transferred to them from the adults who breastfeed them, kiss them, and change their diapers. One fun way to put this is that “e birth of a mammal must be a moment of celebration in the microbial world . . . [as] a new, potential host emerges from the uterus” (Tannock, 1994, p. 1). Some researchers now argue that a healthy gut microbiome contributes to the ability to manage anxiety. For example, microbiota can inuence behavior through vagus nerve signaling and the production of metabolites (Bravo et al., 2011; Cryan & Dinan, 2012). Abnormalities such as low vagus nerve activity are associated with gut abnormalities (Sajdel- Sulkowska et al., 2019). Vagus nerve abnormalities present as symptoms of both prematurity and ASD, suggesting common mechan­isms of inuence even if the core causes are dierent. Similar symptoms include increased prevalence of irritable bowel, cardiovascular abnormalities, and neuro­psychiatric abnormalities (including diculties with socioemotional development). Vagus nerve activity as measured in terms of heart rate variability can be used to estimate regulation by the vagal nerve of the gastrointestinal tract (Sajdel- Sulkowska et al., 2019).