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Your gut eats before you do
'Epigenetic regulation' refers to gene function changes caused by biochemicals not programmed in our own DNA. It appears the epigenetic affect of choline-eating bacteria in our gut is less choline made available to us. Choline is found in high amounts in soybeans, eggs, meat, fish, cauliflower, and milk.
Estimates suggest that only about 10 percent of the U.S. population, including pregnant women, eats the recommended dietary amount of choline. Nutritional demand for the nutrient increases in pregnancy to support epigenetic regulation of healthy cells in a developing fetus. Studies link choline deficiency in human pregnancy to altered behavior in children. When mice were fed a high-fat diet, which induces a range of metabolic diseases in mice, animals with choline-eating microbes gained more abdominal fat and had fattier livers than mice with microbes that couldn't eat choline.
Pregnancy creates a high demand for choline. The team found that pups of mothers with choline-eating gut bacteria exhibited very anxious behaviors. These mother mice also had higher levels of infanticide and obsessive grooming. All behaviors indicating extreme anxiety.
Rey's team suspects 'epigenetic regulation' partly explains these negative outcomes. However, a by-product of bacterial choline metabolism known as TMAO might also be implicated. Some studies report higher dietary choline might increase cardiovascular disease risk as choline can interact with dietary ingredients, such as carnitine, and be converted by intestinal bacteria into trimethylamine (TMA). TMA is then absorbed and converted by the liver into trimethylamine-N-oxide or TMAO, a substance linked to even higher risk for cardiovascular disease. Toxic TMAO might also disrupt epigenetic processes to create problems in metabolism and development. But, adding more choline to a diet might just lead to more TMAO rather than fix a choline deficet.
While Rey's work suggests a complex link between nutrition, gut microbes, and a host's metabolism is vital to being healthy, many questions still remain.
• Gut bacteria compete with the host for choline, decreasing bioavailability
• Microbial choline degradation depletes methyl-donor metabolites
• Microbial choline utilization alters in utero epigenetic programming of the brain
• Mice with choline-consuming gut microbiota display altered behavior
Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.
Keywords: microbiome, choline deficiency, epigenetics, trimethylamine, trimethylamine-N-oxide, gnotobiotic
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Rey's group isolated and bred germ-free mice colonized with specific populations of choline eating microbes to test whether those microbiomes compete with their hosts.
Image Credit: University of Wisconsin-Madison