Nurturing the Early Life Gut Microbiome and Immune Maturation for Long Term Health

Abstract

Early life is characterized by developmental milestones such as holding up the head, turning over, sitting up and walking that are typically achieved sequentially in specific time windows. Similarly, the early gut microbiome maturation can be characterized by specific temporal microorganism acquisition, colonization and selection with differential functional features over time. This orchestrated microbial sequence occurs from birth during the first years of age before the microbiome reaches an adult-like composition and function between 3 and 5 years of age. Increasingly, these different steps of microbiome development are recognized as crucial windows of opportunity for long term health, primarily linked to appropriate immune and metabolic development. For instance, microbiome disruptors such as preterm and Cesarean-section birth, malnutrition and antibiotic use are associated with increased risk to negatively affect long-term immune and metabolic health. Different age discriminant microbiome taxa and functionalities are used to describe age-appropriate microbiome development, and advanced modelling techniques enable an understanding and visualization of an optimal microbiome maturation trajectory. Specific microbiome features can be related to later health conditions, however, whether such features have a causal relationship is the topic of intense research. Early life nutrition is an important microbiome modulator, and ‘Mother Nature’ provides the model with breast milk as the sole source of nutrition for the early postnatal period, while dietary choices during the prenatal and weaning period are to a large extent guided by tradition and culture. Increasing evidence suggests prenatal maternal diet and infant and child nutrition impact the infant microbiome trajectory and immune competence development. The lack of a universal feeding reference for such phases represents a knowledge gap, but also a great opportunity to provide adequate nutritional guidance to maintain an age-appropriate microbiome for long term health. Here, we provide a narrative review and perspective on our current understanding of age-appropriate microbiome maturation, its relation to long term health and how nutrition shapes and influences this relationship.

Intestinal Colonization With Bifidobacterium longum Subspecies Is Associated With Length at Birth, Exclusive Breastfeeding, and Decreased Risk of Enteric Virus Infections, but Not With Histo-Blood Group Antigens, Oral Vaccine Response or Later Growth in Three Birth Cohorts

“…Bifidobacterium longum subspecies are a ubiquitous presence in the gut microbiota of human infants, transmitted vertically from the mother at birth via vaginal delivery or shortly after in the first breastmilk meals and thereupon proliferating by metabolizing the HMOs consumed through subsequent breastfeeding ( 41 , 42 ). Metabolites produced by this fermentation process, such as acetate, formate and lactate, promote epithelial barrier function ( 43 ) and create an acidic environment hostile to bacterial pathogens ( 44 ), while the adhesion of enterocytes to bifidobacterial interacting with pilis and other surface-associated cellular structures trigger some of the first proinflammatory responses, priming the immune system for early development ( 8 , 41 , 45 ). These processes are believed to underly the well-documented associations of intestinal bifidobacterial colonization with numerous health benefits later in infancy and beyond ( 41 ).…”

The Complex Link and Disease Between the Gut Microbiome and the Immune System in Infants

“…The immune system of the intestinal mucosa consists of lymph nodes, lamina propria, and epithelial cells that form a physiological barrier that protects the integrity of the gut ( Shi et al., 2017 ). Innate immune cells use a diversity of PRRs, including Toll-like receptors, NOD-like receptors and leptin-like receptors, to recognize conserved molecular patterns of microbes and signaling of these receptors may then act as developmental triggers for the gut microbiome ( Fulde et al., 2018 ; Price et al., 2018 ; Dogra et al., 2021 ). IL-22 produced by innate lymphoid cells is in a position to induce hRegIIIα production in epithelial cells, which binds to bacterial peptidoglycan carbohydrates and kills Gram-positive target bacteria ( Mukherjee et al., 2014 ; Shi et al., 2017 ).…”

The Role of Nutritional Factors in the Modulation of the Composition of the Gut Microbiota in People with Autoimmune Diabetes

“…Changing the structure, abundance, and eubiotic state of the microbiota may contribute to intestinal and parenteral autoimmune and inflammatory disorders [12,30], which can lead to the occurrence of diseases associated with these conditions. It has been suggested that this condition could be the result of a lack of early stimulation of the immune system by biotic factors, which may interfere with the functioning of the immune system later in life and lead to hypersensitivity, autoimmune diseases, and/or inflammatory diseases [31]. This could explain the fact that there are more and more cases of autoimmune diseases, the occurrence of which cannot always be explained by genetic factors, but rather environmental factors, e.g., T1DM [5].…”

“…Questionable lifestyle and nutritional choices (albeit not always intentional), primarily in developed countries characterized by the West-type diet, may lead to the development of microbiota that lack the immunity and diversity necessary for a balanced immune response. It is believed that this may lead to an increase in autoimmune and inflammatory diseases [31,73]. Increased consumption of junk food has been shown to be associated with less gut microbiome diversity in children with T1DM [74].…”