Importance of the Microbiota in Early Life and Influence on Future Health

The concept of complex crosstalk between the gut and the brain is not new, but rather extends back over the past 2000 years, beginning with philosophers including Hippocrates, Plato, and Aristotle suggesting that the mind and body are fully integrated and inseparable from each other. However, the 19th century saw a period of accelerated investigation into the communication pathways that exist between the gut and the brain in both health and disease, which resulted in advances in treatment and management strategies for diseases in the field of neurogastroenterology. Overviews of the historical investigations leading to the discovery of the gut–brain axis have been provided in several reviews (Cryan et al., 2019; Margolis et al., 2021; Mayer, 2011), which detail the extensive reach and function of these gut–brain communication pathways. In more recent times, the bidirectional communication between the gastrointestinal (GI) system and the brain has been termed the “the gut–brain axis”. This axis is key to the maintenance of host homeostasis via multiple communication pathways and contributions of multiple systems and is also reciprocally influenced by the systems of the body. This idea was discovered in the 1840s by William Beaumont who showed that varying emotional states affect the rate of digestion, thus suggesting that the brain and the gut are communicating. Bidirectional communication pathways allow for the GI tract to impact on nervous system–related functions such as mood, emotion, pain responsivity, stress reactivity, and neurochemistry (Foster et al., 2017; Gao et al., 2019; Huang and Wu, 2021; Huang et al., 2019; Mayer et al., 2014, 2015a), while in turn exerting local effects in the GI tract by affecting motility, secretion, and permeability (Covasa et al., 2019; Moyat et al., 2022; Waclawiková et al., 2022). Most recently, the communication networks of the gut–brain axis have been expanded to reflect the role of the gut microbiota, the hundreds of trillions of microorganisms that reside in the gut, and collectively this communication pathway is now referred to as the “microbiota–gut–brain axis” (Cryan et al., 2019; Morais et al., 2021; Sherwin et al., 2016). The number of microbial cells in the body outnumbers the number of human cells to the order of 1.3:1 (Sender et al., 2016), so it is not surprising that this community of microorganisms has widespread effects on physiology, not just restricted to the GI tract (Contijoch et al., 2019; Cryan and Dinan, 2012; Dinan and Cryan, 2017). While other distinct microbial communities exist both within, and on the surface of organisms, including the oral microbiota (Kilian et al., 2016), pulmonary microbiota (Lynch, 2016), and skin microbiota (Grice and Segre, 2011), the most extensive microbiota population is that of the GI tract (Cryan et al., 2019). These bacteria, eukarya, and archaea have evolved with their hosts over millennia to form a complex and a mutually beneficial relationship (Backhed et al., 2005; Neish, 2009). Some of the physiologically beneficial effects that the microbiota confers to the host include reinforcement of the gut barrier against pathogens (Baumler and Sperandio, 2016; Natividad and Verdu, 2013), regulation of host immunity (Belkaid and Hand, 2014), and energy balance and metabolism (den Besten et al., 2013). The gut microbiota is also pivotal in the communication between the gut and the brain and is implicated in disorders of both (Bastiaanssen et al., 2018; Mayer et al., 2015b; Morais et al., 2021; Wilmes et al., 2021). Here, we will discuss and summarize the importance of the gut microbiota in early life development across the microbiota–gut–brain axis and the ramifications of early life insults on future health. Further, microbiota-targeted therapies against disorders of altered microbiota–gut–brain axis signaling will be explored.