Can the Child’s Diet in the Early Years Shape the Microbiome and Metabolic Health? New Research and Directions

Microbiome Digestion Matters: Maximising the Benefits of Dietary Glycans in Early Life

Dr. Giles Major - Head of Department, Gastrointestinal Health, Nestle Institute of Health Sciences Honorary Associate Professor, School of Medicine, University of Nottingham Switzerland

Key Messages

• Diet is a key determinant of microbiome development during early life, which in itself will determine microbiome composition throughout life
• Glycans resistant to upper gut digestion, such as human milk oligosac¬charides in breast milk, are crucial nutrients for the microbiome and will determine the proliferation of relevant key species to infant health
•  Introduction of other dietary sources of glycan should be graduated to ensure a healthy development trajectory for the switch from infantile to a juvenile microbiome, and thus maintaining immune competence without impact on immune tolerance of dietary proteins 

Abstract

The role of the gut microbiome in human health has long been appreciated especially when enteric pathogens cause illnesses through local and systemic inflammatory responses. Moreover, improvements in genetic sequencing identified colonic microorganisms that traditional culture methods could not. Hence, it rapidly increased our understanding of the microbiome’s structure, function, and less immediate so as more complex influences on health and development.
Each individual has a personal microbiome with its own particular interactions in the bacteria present. Thus, it unravels the complicated relationship between the microbiome and the host health. Factors appearing to mark a ‘healthy microbiome’ include the relative abundance of certain key species that hold together the community of bacteria: the diversity of species, strains and the activity of the genes they carry, as well as the profile of different nutrients and signalling molecules released by the bacteria like short-chain fatty acids (SCFA) acetate, lactate and butyrate.
In early life, the microbiome sequentially develops so that each stage heavily influences the next. It fol lows that promotion of a healthy microbiome in early life is crucial. Maternal health and route of delivery at birth are both recognized as key influences, particularly the effect of early seeding from the skin (during caesarean section) or birth canal. Thereafter, other environmental exposures such as soil, animals, and medication all have an impact. So dominant exposure is diet; and in early life, this signifies breast milk.
The term ‘glycans’ includes the whole range of carbohydrates- from short-chain oligosaccharides to fibers. Human milk oligosaccharides (HMOs) in breast milk are not digested by human enzymes and they represent an important nutrient source for the microbiota, promoting species with the genetic capacity to digest such carbohydrates (CAZymes- carbohydrate active enzymes).
Specific Bifidobacteria can digest HMOs and proliferate in their presence during breastfeeding. Bifidobacteria and Lactobacilli convert HMOsand other oligosaccharides into acetate and lactate which both feed other beneficial bacteria. Additionally, acetate also plays a key role in modulating permeability of the gut epithelium, controlling infant exposure to the digested components of diet and allowing the acquisition of immune tolerance. This means that variations in the HMO profiles that infants consume will affect which bacterial strains proliferate and produce metabolites.
At weaning, the range of dietary exposure increases, including a growth in the types of glycan on which the microbiota can feed. Diet diversity will widen microbiome diversity, adding to the production of butyrate to nourish the gut epithelium, but there may be good reasons to ensure that the development of this microbiota maturation follows a controlled trajectory. Therefore, continued exposure to acetate during the weaning period, rather than a complete switch to butyrate, may support immune exposure and avoid the induction of atopic responses in later years. So continued consumption of HMOs during weaning may be one strategy to ensure that acetate levels are maintained.
Overall, understanding the optimal trajectory for microbiome maturation and how to support the switch from infantile to juvenile microbiome may enhance dietary advice in early life. Specifically, a graduated progression from simpler oligosaccharides like HMOs to a diet with diverse range of fibre sourceswill promote microbiota diversity- CAZyme capacity and micro biome digestive health. 
 

References

1. Stewart, C.J., Ạjami, N.J,, O’Brien, J.L et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 562,583-588 (2018). https:// doi.org/10.1Q38/s4158gr018-0617-x
2. Dogra SK, Kwong Chung c, Wang D,Sakwlnska O, Colombo Mottaz S, Sprenger N. Nurturing the Early Life Cut Microbiome and Immune Maturation for Long Term Health. Microorganisms. 2021;9(10):2110. Published 2021 Oct 7. https://doi:10.3390/microorganisms9102n0
3. Roswall J, Olsson LM, Kovatcheva-Datchary p et al. Developmental trajectory of the healthy human gut microbiota during the first 5 years of life. Cell Host Microbe. 2021 May 12;29(5):765-776.e3. https://doi:10.1016/lxhom.2021.02.021 

Crucial Role of Early Life Nutrition in Shaping Childhood and Adult Health – a Metabolic Perspective

Yann Ravussin, Ph.D - Lecturer & Staff, Université de Fribourg, Department Endocrinology, Metabolism and Cardiovascular Systems, Medicine Section LEAN – Laboratory of Energetics and Advanced Nutrition Switzerland

Key Messages

• Accumulating evidence suggests that time windows in early childhood can directly affect adult metabolic health and the transition from mother’s milk to solid food (complementary feeding) likely represents such an important timeframe
• Preclinical and clinical data show that differences in glycemic index and macronutrient composition of foods available during this time window have affect subsequent metabolic parameters
•  Infant cereals represent an important first food and reformulation of such complementary feeding may provide a crucial step in prevention of certain adult chronic diseases 

Abstract

Introduction of solid foods (i.e. weaning or complementary feeding) in early childhood is an important step in normal infant development and may represent a crucial time window involved in metabolically programming an individual in later life [1]. Data suggests that such early developmental windows play a crucial and causal role in the predisposition of chronic diseases later in life [2]. For example, the Developmental Origin of Health and Disease Hypothesis (DOHaD) looks into the reprogramming caused by certain intrauterine stressors which has been directly linked to altered future metabolic states with epigenetic changes playing a pivotal role [3].
While intrauterine stresses (e.g. maternal diabetes status, maternal over- or under nutrition, hormonal changes) were linked to future metabolic disturbances in both animal models and humans, less is understood during post-natal early childhood events such as weaning. To be exact, the timing of complementary feeding and the type of food introduced (macro- and micronutrient quality and quantity) are currently being explored [4].
Preclinical studies using mice with humanized beta cells show that diets of different glycemic indexes have direct effects on glucose disposal capacity by altering the number of insulin positive cells. In fact, a high glycemic (HG) diet offered at weaning triggers seemingly increased pancreatic maturation, and potentially priming the animal in being able to better respond to glucose challenges in later life- thus serving as a proof of principle in the potential importance of this time period.
In our own studies, we clearly show that infusion of sufficient liquid calories can increase beta cell proliferation even in adult animals showing clear adult plasticity [5] while the other groups have shown that the number of calories available during the suckling period (by altering litter sizes in rodent models) directly affects the propensity to develop obesity and diabetes later on [6]. Finally, clinical data in a prospective, randomized, single blind, controlled, 2 arm parallel group trial of healthy infants aged 6 months at enrollment showed that providing a lower glycemic index mix of follow-up formula (FuF- lower protein with 100% lactose) and a reformulated infant cereal (IC - higher dietary fiber, higher fat, lower refined cereals, and increased plant-based proteins) had positive impacts on glycemic control.
 

References

[1] Saavedra, J.M. and A. Dattilo, Early nutrition and long-term health : mechanisms, consequenc-
es, and opportunities. Woodhead Publishing series in food science, technology and nutrition. 2017, Amsterdam: Elsevier/Woodhead Publishing. xliv, 576 pages.
[2] Fewtrell, M., et al., Complementary Feeding: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition. J Pediatr Gastroenterol Nutr, 2017. 64(1): p. 119-132.
[3] Bianco-Miotto, T., et al., Epigenetics and DOHaD: from basics to birth and beyond. J Dev Orig Health Dis, 2017. 8(5): p. 513-519.
[4] Caroli, M., et al., Recommendations on Complementary Feeding as a Tool for Prevention of Non-Communicable Diseases (NCDs)-Paper Co-Drafted by the SIPPS, FIMP, SIDOHaD, and SINUPE Joint Working Group. Nutrients, 2022. 14(2).
[5] Ravussin, Y., et al., Evidence for a Non-leptin System that Defends against Weight Gain in Overfeeding. Cell Metab, 2018. 28(2): p. 289-299 e5.
[6] Parra-Vargas, M., et al., Size Does Matter: Litter Size Strongly Determines Adult Metabolism in Rodents. Cell Metab, 2020. 32(3): p. 334-340.