What is already known
A mother’s poor diet can increase her offspring’s risk of developing severe lower respiratory infections, a lead cause of childhood mortality. But although it is known that dietary fiber can change the composition of the gut microbiota, how the maternal diet influences the risk of respiratory infections remains unclear.
What this research adds
Working in mice, researchers have found that a maternal diet low in fiber increases the severity of lower respiratory infections — likely as a result of altered immune system responses. A low-fiber diet changes the composition of the maternal milk microbiota and in turn that of the infant gut microbiota. These alterations reduce the production of Flt3L, a molecule that increases the number of immune cells by activating the cells’ progenitors. Pups colonized with propionate-producing bacteria or those supplemented with propionate are protected against severe lower respiratory infections.
Conclusions
The findings suggest that the diet-induced changes in the gut microbiota confer protection against respiratory infections by regulating the development of key components of the immune system.
A mother’s poor diet can increase her offspring’s risk of developing severe lower respiratory infections, a lead cause of childhood mortality. Now, research done in mice shows that the maternal diet can change the infant gut microbiota in ways that confer protection against respiratory infections. The diet-induced changes in the gut microbiota regulate the development of key components of the immune system, the study shows.
The findings, published in Immunity, could help to develop interventions that protect children from inflammation-mediated conditions such as respiratory infections and asthma.
It is known that dietary fiber influences the composition of the gut microbiota in ways that increase the levels of beneficial immunomodulatory metabolites such as short chain fatty acids. These metabolites activate key immune cells such as dendritic cells, which boost immune responses by showing antigens to other cells of the immune system. The metabolites also modulate regulatory T (Treg) cells, a type of T cells that suppress immune responses, thus maintaining self-tolerance.
However, it is unclear how the maternal diet influences the risk of respiratory infections. To address this question, Simon Phipps at QIMR Berghofer Medical Research Institute and his colleagues infected infant mice with the murine equivalent of respiratory syncytial virus — a common, contagious virus that causes infections of the respiratory tract in humans. The mice were born to mothers that received either a low-fiber or a high-fiber diet.
Milk microbiota
Pups reared by mothers fed a low-fiber diet had increased viral load in their airways and produced lower levels of a key antiviral immune molecule. These pups also developed the hallmark features of a severe lower respiratory infection, including excessive inflammatory response and tissue damage.
Mice reared by mothers fed a low-fiber diet showed decreased numbers of neonatal plasmacytoid dendritic cells, a specialized subset of dendritic cells that initiate antiviral immunity. They also had fewer Treg cells than control mice, the researchers found.
The content of dietary fiber was positively associated with the levels of the short chain fatty acids propionate and acetate in the mother’s feces. A low-fiber diet also changed the composition of the maternal milk microbiota and in turn that of the infant gut microbiota, the team found.
Disease resistance
Further experiments showed that the diet-induced changes in the pups’ gut microbiota reduced the production of Flt3L, a molecule that increases the number of immune cells by activating the cells’ progenitors.
Pups colonized with propionate-producing bacteria isolated from the milk of mothers fed a high-fiber diet were protected against severe lower respiratory infections, the researchers found. Pups supplemented with propionate were also less likely to develop those infections.
Manipulating the maternal diet during pregnancy and before weaning, or supplementing infants with prebiotics or probiotics, may help to confer resistance to inflammatory diseases, including acute respiratory infections, asthma and allergies, the authors say.
