Group | Microbiota-Targeted Interventions

With roughly 150 million children affected, undernutrition remains one of the most important public health threats. Nevertheless, we lack efficient treatments to allow chronically malnourished (stunted) children regain normal growth or prevent them from relapsing after treatment for acute undernutrition (wasting). This treatment failure is due to the fact that we know little about the underlying pathophysiological mechanisms.

Undernutrition is a complex entity entailing at the same time climatic, socio-economic and biological factors. The underlying causes of stunting range from inadequate food to poor hygiene and repeated infections. In the last years evidence has accumulated that a chronic, inflammatory syndrome of the small intestine, called environmental enteric disease (EED), also plays a major role in this syndrome. EED seems to be the result of a continuous exposure to a highly microbiologically contaminated environment and is characterized by an increase in the permeability of the small intestine and influx of immune cells into the gut epithelium. EED is also associated with changes in the small intestinal microbiota.

Our work is centered on the role of the microbiota and the gut ecosystem in different forms of malnutrition in order to contribute to the understanding of the syndromes and harness then this knowledge to develop powerful interventions strategies and treatments.

To this purpose, we perform clinical projects and analyze the underlying molecular mechanisms using in vitro and in vivo models.

Approach and Expertise

In collaboration with the Jigjiga University and the Armauer Hansen Research Institute in Ethiopia as well as the Lao Tropical and Public Health Institute in Lao PDR, we are currently conducting clinical studies in the Somali Region of Ethiopia as well as Lao PDR and also use human samples from a previous study in Madagascar and the Central African Republic (collected through the Afribiota project, a collaboration with Institut Pasteur, Institut Pasteur de Madagascar and Institut Pasteur de Bangui).

To elucidate the dysbiosis and understand the underlying pathophysiology, we apply sequencing techniques as well as (anaerobic) culture of bacteria, in vitro and cell culture assays and animal models.

Jakob Zinsstag

Jakob Zinsstag, Professor, PhD, DVM

Pastobiome Project

We could recently show that the intestinal microbiota is changed in stunted children, and displays a specific microbial signature likely responsible for the observed dysbiosis. However, we don’t know if the observed signatures are conserved in regions where the diet consists of different staple foods or if they are specific to each context (“global vs. regional microbiota changes”) and if it is conserved in different forms of undernutrition. We will address these questions in the Pastobiome project, analyzing the microbiota of pastoralist children in the Somali Regional State of Ethiopia.

Nutrition-Related Microbial Dysbiosis in Early Life

Malnutrition in pregnancy and childhood is increasingly recognized as important risk factor for obesity and metabolic disorders in adults “dual burden of malnutrition”. It is suspected that the microbiota plays a major role in this phenomenon; however, the exact molecular causes and consequences are yet to be elucidated. We address these questions in a human cohort, which we will recruit together with the Lao Tropical and Public Health Institute within an existing multigenerational cohort (VITERBI). In addition, we will experimentally test the underlying causal relationships in cell and animal models.

 

Microbiota-Targeted Interventions for Child Undernutrition

In collaboration with Dr. Lisa Maier’s group at the University of Tübingen and with financial support from the Bill and Melinda Gates Foundation, we will develop new tools to rapidly identify members of the human microbiota, establish a child microbial strain biobank and screen for compounds that hamper the growth of health-deteriorating and promote the growth of health-promoting bacterial strains. These microbiota-modulating compounds can then be combined in an integrated approach with the existing nutritional rehabilitation schemes to better tackle childhood undernutrition in the poorest regions of this world. Read more

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