Bacterial proteins present in the circulation may activate feeding-related brain circuitry. This image shows neurons (c-Fos, green) in rat brain activated by proteins from “stationary phase” E. coli. (Twenty minutes after nutrient supply, E. coli shift from stabilized exponential growth to the stationary phase while altering their proteomic profile.) The neurons are surrounded by nerve terminals (calcitonin gene-related peptide, red) originating from anorexigenic brainstem projections. [J. Breton, N. Lucas, and D. Schapman]
When you join a Thanksgiving feast or any other meal, you don’t come alone. You bring your gut microbes with you. And they seem to have a say over how much food you’ll consume. Twenty minutes after a meal, gut microbes produce proteins that trigger a host’s biochemical satiety mechanisms, suppressing appetite and reducing food intake. Although these proteins originate in gut microbes such as Escherichia coli, they end up influencing neuronal circuits in the host’s brain.
This finding comes from a study (“Gut Commensal E. coli Proteins Activate Host Satiety Pathways following Nutrient-Induced Bacterial Growth”) that appeared November 24 in Cell Metabolism. This study showed that in mice and rats, nutrient availability stabilizes the exponential growth of E. coli within 20 minutes. This effect is accompanied by proteome changes that induce satiety in the host.
The study also showed how the proteins produced by gut microbes could, when injected into mice and rats, act on the brain to reduce appetite. Overall, the study suggests that gut bacteria may help control when and how much we eat.
“[Intestinal] infusions of E. coli stationary phase proteins increased plasma PYY and their intraperitoneal injections suppressed acutely food intake and activated c-Fos in hypothalamic POMC neurons, while their repeated administrations reduced meal size,” wrote the authors. “ClpB, a bacterial protein mimetic of α-MSH, was upregulated in the E. coli stationary phase, was detected in plasma proportional to ClpB DNA in feces, and stimulated firing rate of hypothalamic POMC neurons.”
Essentially, the new evidence coexists with current models of appetite control, which involve hormones from the gut signaling to brain circuits when we're hungry or done eating. The bacterial proteins—produced by mutualistic E. coli after they've been satiated—were found for the first time to influence the release of gut-brain signals (such as GLP-1 and PYY) as well as activate appetite-regulated neurons in the brain.
“There are so many studies now that look at microbiota composition in different pathological conditions but they do not explore the mechanisms behind these associations,” said senior study author Sergueï Fetissov, Ph.D., of Rouen University and INSERM's Nutrition, Gut and Brain Laboratory in France. “Our study shows that bacterial proteins from E. coli can be involved in the same molecular pathways that are used by the body to signal satiety, and now we need to know how an altered gut microbiome can affect this physiology.”
The investigators also reported that they developed an assay that could detect the presence of one of the “full” bacterial proteins, called ClpB in animal blood. Although blood levels of the protein in mice and rats detected 20 minutes after meal consumption did not change, it correlated with ClpB DNA production in the gut, suggesting that it may link gut bacterial composition with the host control of appetite. The researchers also found that ClpB increased firing of neurons that reduce appetite. The role of other E.coli proteins in hunger and satiation, as well as how proteins from other species of bacteria may contribute, is still unknown.
“We now think bacteria physiologically participate in appetite regulation immediately after nutrient provision by multiplying and stimulating the release of satiety hormones from the gut,” Dr. Fetisov added. “In addition, we believe gut microbiota produce proteins that can be present in the blood longer term and modulate pathways in the brain.”