A microbial perspective of human developmental biology

Abstract

When most people think of human development, they tend to consider only human cells and organs. Yet there is another facet that involves human-associated microbial communities. A microbial perspective of human development provides opportunities to refine our definitions of healthy prenatal and postnatal growth and to develop innovative strategies for disease prevention and treatment. Given the dramatic changes in lifestyles and disease patterns that are occurring with globalization, we issue a call for the establishment of 'human microbial observatories' designed to examine microbial community development in birth cohorts representing populations with diverse anthropological characteristics, including those undergoing rapid change.

Figure 1. Representation of abundant HMOs present in milk and strategies employed by infant gut microbiota for their degradation

(A) Secretor status and HMO composition. HMO structures that are most abundant in secretors are indicated by the blue arrow, while those that are most abundant in the breast milk of non-secretors are indicated by the red arrow. Structures at the intersection are found in both secretor and non-secretor mothers in similar abundances. The structures of these HMOs, along with their glycosidic linkages, are described by the inset key. (B) Most strains of Bifidobacterium use an ‘internalize, then degrade’ strategy where HMO structures are first imported using ABC transporters and degraded by intracellular glycoside hydrolases (GH). (C) Strains of Bacteroides typically employ an ‘external degradation’ strategy for HMO structures that involves cell surface associated carbohydrate binding proteins and secreted glycoside hydrolases encoded by polysaccharide utilization loci (PULs) that have features similar the prototypic starch utilization system (Sus) of Bacteroides thetaiotaomicron. This external degradation can result in ‘cross-feeding’ of secondary consumers in the infant gut microbiota.

Figure 2. Discovery pipeline for characterizing the functional properties of developing human microbial communities

Gnotobiotic animals can be employed as preclinical models for determining the effects of various states of microbial community development on host developmental biology.