Technical University of Denmark: The consequences of malnutrition are inheritable

Damage to the microbiome caused by malnutrition is transmitted from mothers to newborns and has lifelong consequences for their physical and intellectual development.
Infant malnutrition damages the composition of intestinal bacteria, the microbiome. It has life-long consequences on the physical and intellectual development of affected children. Using pigs and mice models, Professor Bernard Henrissat from DTU Bioengineering in collaboration with the Washington University School of Medicine (USA), shows that damage to the microbiome and the metabolic consequences of malnutrition are transmitted from mothers to newborns. The study documents which mechanisms in enzymes’ breakdown of carbohydrates in the diet are damaged by malnutrition.

“The study shows that newborn pigs, born to sows that have been exposed to diet restriction during pregnancy, are born with growth defects and their intestinal bacteria produces less butyrate and less enzymes for the digestion of complex carbohydrates. These piglets have a harder time digesting food, and the damage to their microbiome does not disappear when receiving a normal diet,” says Bernard Henrissat.

However, having identified the precise enzymes that were most affected by undernutrition opens the possibility to repair microbiomes damaged by malnutrition or by other pathologies.

Classification of enzymes
The study is published in the acclaimed international journal PNAS, and contributes a new analytical model of the enzymes involved in the breakdown of carbohydrates in animals and humans in the diet. For 30 years, Bernard Henrissat has built up a classification that makes it possible to distinguish between the enzymes in the microbiome that break down complex carbohydrates, so-called CAZymes. Using previous knowledge about the importance of the individual enzymes for the breakdown of nutriments, the researchers were able to show that the newborns smaller size and weight, and subsequent slow growth, was linked to the composition of their intestinal bacteria.

Algorithm for intestinal bacteria
The analytical model in the experiment is based on an algorithm that can identify information-rich CAZymes in a large number of microbiome-related data acquired during the growth of the animals. By entering the many data in a computer model and processing them in the algorithm, the researchers were able to identify which groups of enzymes were missing in the experimental animals’ metabolism of nutrition.

Bernard Henrissat estimates that the analytical model and classification of CAZymes in the gut can provide clues about what is important to optimize for the growth of pigs, especially in the weeks after birth. The researchers are now working in new experiments to test whether it is possible to affect the microbiome, and perhaps even repair microbiome injuries in animals and humans, by organizing a diet that increases the occurrence of certain CAZymes in the intestine, and thereby improving the degradation of complex carbohydrates.