Microbiota-Gut-Brain Axis Regulation of Adult Hippocampal Neurogenesis

Abstract

The birth, maturation, and integration of new neurons in the adult hippocampus regulates specific learning and memory processes, responses to stress, and antidepressant treatment efficacy. This process of adult hippocampal neurogenesis is sensitive to environmental stimuli, including peripheral signals from certain cytokines, hormones, and metabolites, which can promote or hinder the production and survival of new hippocampal neurons. The trillions of microorganisms resident to the gastrointestinal tract and collectively known as the gut microbiota, also demonstrate the ability to modulate adult hippocampal neurogenesis. In doing so, the microbiota-gut-brain axis can influence brain functions regulated by adult hippocampal neurogenesis. Unlike the hippocampus, the gut microbiota is highly accessible to direct interventions, such as prebiotics, probiotics, and antibiotics, and can be manipulated by lifestyle choices including diet. Therefore, understanding the pathways by which the gut microbiota shapes hippocampal neurogenesis may reveal novel targets for non-invasive therapeutics to treat disorders in which alterations in hippocampal neurogenesis have been implicated. This review first outlines the factors which influence both the gut microbiome and adult hippocampal neurogenesis, with cognizance that these effects might happen either independently or due to microbiota-driven mechanisms. We then highlight approaches for investigating the regulation of adult hippocampal neurogenesis by the microbiota-gut-brain axis. Finally, we summarize the current evidence demonstrating the gut microbiota’s ability to influence adult hippocampal neurogenesis, including mechanisms driven through immune pathways, microbial metabolites, endocrine signalling, and the nervous system, and postulate implications for these effects in disease onset and treatment.

The gut microbiota is an emerging target for improving brain health during ageing

“…Hippocampal neurogenesis is influenced by the gut microbiota (Guzzetta et al, 2022;Ogbonnaya et al, 2015), and is well characterized to decline with ageing (Kozareva, Cryan, & Nolan, 2019), suggesting there are underlying age-driven factors that may supersede how an individual responds to a microbial community (Wilmanski, Gibbons, & Price, 2022). Overall, these studies highlight that there are functional differences in the gut microbiota from aged individuals which may be contributing to the decline in cognition and altered neurobiology that occurs during ageing.…”

“…Investigations into these pathways, along with the use of germ-free (GF) rodents, which completely lack all microbes, and direct gut microbiota manipulation, such as antibiotic treatment, faecal microbiota transplantation and microbiota administration, have enabled a deeper understanding of how the gut microbiota influences biological functions in its host, including in the brain. Critically, the gut microbiota influences the blood–brain barrier (Braniste et al, 2014), neurochemistry and cellular functions in the brain, such as immunity and neuroplasticity (Erny et al, 2015; Guzzetta et al, 2022; Mossad and Blank, 2021; Ogbonnaya et al, 2015; Parker et al, 2022; Rei et al, 2022; Scott et al, 2017; Spichak and Guzzetta, 2018) and has been preclinically shown to modulate cognitive function during ageing (Boehme, Guzzetta and Bastiaanssen et al, 2021; Mossad et al, 2021), and neurodegeneration (Erny et al, 2021). Taken together, the gut microbiota plays a crucial role in supporting healthy cognition and neurological functions of its host, including active participation in important aspects of brain ageing.…”

The Role of Microbiome in Psychiatric Diseases (Insomnia and Anxiety/Depression) with Microbiological Mechanisms

“…Additionally, serotonin and 5-HIAA levels in adult GF mice were not increased by introducing bacteria from previously colonized animals into their microbiome. [36,37] 5 Advanced Gut & Microbiome Research pathogen-free microbiota was given to GF female mice after week 10, anxiety-like behaviors did not return, in contrast to when specific bacterial strains were given at birth and three weeks later [45]. Additionally, Hooks et al showed that giving GF mothers a vaccine prior to childbirth completely reversed the stress response in adult offspring.…”

Mechanisms underlying the effect of voluntary running on adult hippocampal neurogenesis

“…In contrast, recurrent spontaneous seizures lead to dramatically reduced neurogenesis (Chen et al, 2020; Hattiangady et al, 2004; Kralic et al, 2005). High‐fat and high‐sugar diets inhibit neurogenesis, but diets enriched with polyphenols and polyunsaturated fatty acids increase neurogenesis (Guzzetta et al, 2022; Poulose et al, 2017; Stangl & Thuret, 2009).…”