Milk Oligosaccharides Prevent Stressor‐Induced Alterations in the Colonic Mucosa‐Associated Microbiota and Animal Behavior: Evidence for Effects on the Gut‐Brain Axis

There are extensive bidirectional interactions between the gut microbiota and the central nervous system (CNS), and studies demonstrate that stress significantly alters gut microbiota community structure. We tested whether milk oligosaccharides would prevent stressor‐induced alterations in gut microbial community composition and anxiety‐like behavior. Mice were fed standard laboratory diet, or laboratory diet containing milk oligosaccharides 3″Sialyllactose (3SL) or 6″Sialyllactose (6SL) for two weeks prior to being exposed to either a social disruption stressor or a non‐stressed control condition. Stressor exposure significantly changed the structure of the colonic mucosa‐associated microbiota, as indicated by changes in beta diversity. The stressor also resulted in anxiety‐like behavior in both the light:dark preference and open field tests. This effect was associated with a reduction in neuronal proliferation in the dentate gyrus as indicated by doublecortin immunostaining. These effects were not evident in mice fed milk oligosaccharides; stressor exposure did not significantly change microbial community structure in mice fed 3SL or 6SL. In addition, 3SL and 6SL attenuated the stressor‐induced anxiety‐like behavior and prevented the reduction in doublecortin staining. These studies indicate that milk oligosaccharides can prevent the effects of stress on the microbiota and on anxiety‐like behavior, as well as modify the gut microbiota‐brain axis. Supported by Mead Johnson Nutrition.