Microbiota in development and stress management

Abstract

The gut microbiota plays a significant role in health and development from birth and continues to affect several processes throughout life. The infant gut is unstable, and colonisation is influenced by a variety of factors. Many of these factors can contribute to an altered microbiota profile in infancy which can subsequently be associated with negative consequences later in life, due to interactions between the microbiota and the brain. The microbiota-gut-brain axis is a bi-directional communication network, which allows the microbiota to affect and influence a variety of psychological processes including mood and cognition. There is evidence to support the co-maturation of the infant brain with the early gut microbiota, and alterations in this parallel sequential maturation have been associated with long-term effects on brain signalling, immune, and metabolic function and mental health. While many aspects of the microbiota-gut-brain axis are not covered in this thesis, an examination of participants from infancy to adulthood and a study of aged mice provides an insight into these populations. This thesis explores many of the early factors which contribute to gut microbiota disturbances and investigates the long-term consequences associated with these early microbiota maturation disruptions. Following on from this, a potential strategy to positively influence gut and brain health is considered. In Chapter 1, the use of probiotics and prebiotics as modulators of gut health are discussed, including methods of use, and previous investigations. Chapter 2 examines the microbiota-gut brain axis and details specific mechanisms involved in signalling pathways between the gut and the central nervous system (CNS). Chapter 3 focuses on the gut microbiota composition of infants up to 24 weeks old who have been delivered by C-section and have received antibiotic treatment in the first four days of life. This observational study explores the immediate consequences of these perinatal factors on the gut microbiota colonisation pattern, showing significantly different microbiota profiles between infants born vaginally, those born by C-section, and those who were also born by C-section and were treated with antibiotics. In Chapter 4, the long-term consequences of mode of delivery are examined. The gut microbiota composition of a cohort of 18-24-year-old males who were born by C-section is analysed and compared with those who were born vaginally. This investigation shows the significance of an altered microbiota during infancy on immune-brain signalling processes, as participants who were born by C-section exhibit increased vulnerability to psychological stress and anxiety. Chapter 5 investigates the effects of a potential psychobiotic, Bifidobacterium longum 1714™, on stress, mood, and cognition in a healthy population. No differences are noted in gut microbiota profile, mood, or cognition in response to the intervention. However, a statistically significant difference is seen in sleep quality in participants consuming the strain, suggesting that this microbe may be beneficial to maintain sleep quality during periods of stress. In Chapter 6, the caecal microbiota composition of aged (20-21 months old) and young mice (2-3 months old) was examined. The behavioural and psychological profiles of these mice were also assessed, as well as gut permeability and inflammation. It was found that older mice showed increased anxiety-like behaviours and reduced memory capabilities when compared to young mice. Additionally, the caecal microbiota profile differed between the two groups in terms of composition and gut permeability. This suggest that caecal microbiota changes seen in the aged mice are associated with aged-related behavioural and cognitive impairments.