Adolescence and Aging: Impact of Adolescence Inflammatory Stress and Microbiota Alterations on Brain Development, Aging, and Neurodegeneration

Abstract

Puberty/adolescence is a critical phase during neurodevelopment with numerous structural, neurochemical, and molecular changes occurring in response to genetic and environmental signals. A consequence of this major neuronal reorganizing and remodeling is a heightened level of vulnerability to stressors and immune challenges. The gut microbiota is a fundamental modulator of stress and immune responses and has been found to play a role in mental health conditions and neurodegenerative disorders. Environmental insults (stress, infection, neuroinflammation, and use of antibiotics) during adolescence can result in dysbiosis subsidizing the development of brain disorders later in life. Also, pubertal neuroinflammatory insults can alter neurodevelopment, impact brain functioning in an enduring manner, and contribute to neurological disorders related to brain aging, such as Alzheimer's disease, Parkinson's disease, and depression. Exposure to probiotics during puberty can mitigate inflammation, reverse dysbiosis, and decrease vulnerabilities to brain disorders later in life. The goal of this review is to reveal the consequences of pubertal exposure to stress and immune challenges on the gut microbiota, immune reactivity within the brain, and the risk or resilience to stress-induced mental illnesses and neurodegenerative disorders. We propose that the consumption of probiotics during adolescence contribute to the prevention of brain pathologies in adulthood.

Keywords: Adolescence; Microbiota; Neurodegeneration; Neuroinflammation; Puberty.

Figure 1.

Microbiota diversity and neuronal complexity throughout life span with emphasis on the critical adolescence window. The core microbiota undergoes a dynamic shift across the life span. After initial colonization during infancy and birth, the gut microbiota continues to develop throughout childhood and adolescence. A less diverse microbiota is found in adolescent children in comparison with adults. As adulthood approaches, the gut microbiota stabilizes and becomes more diverse. With aging, microbiota diversity and stability decline. Shaping of the microbiota happens in parallel with neurodevelopment and they have similar critical developmental windows. Synaptogenesis begins at post-birth and synaptic density increases; the maximum density is attained at approximately 2 years of age. Then synaptic refinement and elimination occur in the human brain leading to reach the adult levels by mid-adolescence. During the critical developmental window (adolescence), there is an increased vulnerability to external stressors. Early adolescence is a key phase of neurodevelopment when major neuronal rewiring synaptic pruning or elimination of extra synapses occurs. A consequence of this important neuronal rewiring during adolescence is a high degree of vulnerability to different pathological stressors (inflammation, stress ….). The pubertal vulnerability of the brain to environmental stressors coincides with instability and immaturity of gut microbiota exacerbating the susceptibility of the brain to aberrant changes that may lead to the onset of brain disorders later in life (neurodegenerative or neurodevelopment disorders).