Persistent gut microbiota immaturity in malnourished Bangladeshi children

Abstract

Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM) but incomplete restoration of healthy growth remains a major problem1,2. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S rRNA datasets generated from monthly fecal samples obtained from a birth-cohort of children, living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a ‘relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ that compare development (defined here as maturation) of a child’s fecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors including diarrhea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.

Identifying strains that contribute to complex diseases through the study of microbial inheritance

“…Severe acute undernutrition is associated with significant relative microbiota immaturity that is only partially ameliorated following commonly used nutritional interventions. This immaturity is also evident in less severe forms of undernutrition and correlates with anthropometric measurements (17). These findings provide a microbial measurement of postnatal development that can be applied to individuals who are, or who are not, biologically related to one another and suggest that healthy growth is dependent upon normal maturation of the gut community.…”

The Porosity of Autonomy: Social and Biological Constitution of the Patient in Biomedicine

“…Further, these biological and social relations are correlated in terms of their impacts on individual health. Some microbial biologists have claimed that our microbiota can provide us with a reliable measure for malnourishment in postnatal development, and thus, also, a more robust parameter of judging the efficacy of therapeutic food interventions (Subramanian et al 2014). Thus, the autonomous patient is certainly not an atomistic and socially isolated person, but causally and constitutionally constructed both in terms of social and biological relations.…”

The Microbiome: a Key Player in Human Health and Disease

“…Obesity [15], insulin resistance [16] and khwashiorkor [17] are examples for which a correlation between microbial dysbiosis and the clinical state has been demonstrated. Further, in genetically susceptible hosts, the transplantation of fecal microbiota from healthy donors to patients resulted in clinical improvement.…”