HudsonAlpha ED Guidebook 2021_22

NEW FINDINGS — INFECTIOUS DISEASE

Gut microbes coordinate immune responses in mice

Most animals follow 24 hour circadian patterns, with periods of activity followed by times of rest. Mealtimes follow these patterns, with people generally eating during the day while animals like mice eat primarily at night. Inside the intestines of many animals, microbes synchronize their own activity to match the feeding patterns of their host and availability of nutrients. A recent study suggests that in mice this synchronization sig- nals the immune system to be on the alert for harmful bacteria hitching a ride on the most recent meal. Researchers began by tracking the levels of REG3G, an antimicrobial protein mice secrete from their small intestines. Levels peaked at night, when the mice were feeding. Intrigu- ingly, protein levels were consistently low in mice lacking a gut microbiome, suggesting a connection between intestinal bacteria and the antimicrobials. When scientists looked for cyclical patterns among gut microbes, they discovered that segmented filamentous bacteria attached to the lining of mice intestines each night, presumably to extract nutrients from the forthcoming feeding.

A spacey new bacteria As part of an ongoing microbial tracking and sequencing experiment, environmental samples from the International Space Station have identified a previously unknown species of bacteria closely related to Methylobacterium. Earth-bound methylobacterium species, often found in soil and freshwater, are gram negative, rod-shaped bacteria involved in nitrogen fixation, protecting against plant pathogens, and promoting plant growth. The discovery of novel plant-associated bac- teria on the ISS is perhaps not surprising as ISS astronauts have been growing small amounts of food on the station for years. Researchers suspect the novel bacteria may be derived from bacterial strains often associated with rice that may have hitched a ride to the space station with either a seed or a food shipment. This discovery could prove valuable as microbes that promote plant growth are critically import- ant for long-term human space exploration. They may play a future role in keeping plants healthy for oxygen and food production under the extreme conditions of long-term space travel and colonization. REFERENCE: Bijlani S. et al. Methylobacterium ajmalii sp. Nov., Isolated From the International Space Station. Frontiers in Microbiology (2021) 12:639396. DOI: 10.3389/ ficb.2021.639396. Microbiome-friendly food benefits undernourished children New research has uncovered a potential link between the gut bacteria of malnourished children and their ability to recover from the effects of starvation. Using fecal samples, researchers had previously com- pared the intestinal microbiome of healthy children to those suffering frommoderate to severe malnutrition, noting the gut biomes of un- dernourished children appeared 'stunted' in development. When gut microbes from undernourished children were transferred to mice, the mice developed metabolic dysfunctions. Like the children, the mice broke down amino acids for energy rather than sugars and their rate of weight gain and bone growth slowed. In a follow-on small human clinical trial, researchers monitored 118 children under age 2 who had moderate malnutrition. Half received the standard calorie-dense supplemental food. The other half received a different supplement containing foods selected to nourish the gut microbiome. Both supplemental foods used locally available ingredients, a critical feature for long-term implementation. Even though the microbiota-directed food regime contained fewer total calories, those children gained more weight and grew more rapidly than the group receiving the standard food supplement. The microbi- ome-nourished children also had increased levels of blood proteins associated with bone growth and brain development. Follow up studies are needed to determine if these short-term gains offset the effects of early life malnutrition. REFERENCE: Chen R.Y. et al. A Microbiota-Directed Food Intervention for Undernourished Children. New Engl J Med (2021) 384:1517-1528. DOI: 10.1056/NEJ- Moa2023294.

Through a series of experiments, the research team deter- mined that this bacterial attachment activates a host immune response designed to heal the bacterial damage to the lining of the gut. Secreting REG3G is part of this response. The REG3G helps neutralize any foreign bacteria present in the food, and serves as the first line of defense against food-based infection. This is the first time gut microbiota have been clearly linked to the innate immune response. The mouse gut uses bacterial behavior to anticipate the 'riskiest' time of day and prepare the immune defense. From a resource perspective, it’s costly to produce antimicrobial molecules. Cellular energy can be saved by making them only when they are likely to be needed. It is unclear if similar relationships exist for human intestinal/ immune interactions. The researchers note that chronic sleep disruption in people is tied to increased susceptibility to infec- tion. Segmented filamentous bacteria do attach to the human gut lining, but it is not known if attachment follows a circadian cycle. If humans do have a connection between gut microbiome and immune response, that knowledge may reshape the deliv- ery and timing of antibiotics, vaccines and immune-modulating medications. REFERENCE: Brooks II J.F. et al. The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock. Cell (2021) 184:P4145-4167.E12 DOI: 10.1016/j.cell.2021.07.001.

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