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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development


Your gut eats before you do

"Gut bacteria get to use a lot of your food before you do, you get their leftovers... "

According to Federico Rey, professor of bacteriology at the University of Wisconsin-Madison: "Gut bacteria get to use a lot of our food before we do. We eat their leftovers or their waste." The problem, explains Rey, is that when our microbiome, those microorganisms that share our body, eat we don't get access to the nutrients first, they do.

The human body contains over 10 times more microbial cells than human cells, yet our entire microbiome can weigh less than 200 grams, although some biomes get as large as 3 pounds! Some doctors and scientists regard the human microbiome as another "organ". Even though its existence wasn't recognized until the late 1990s, our microbiome is now recognized to have potentially overwhelming impact on our health. Now Rey's research reveals that mice with high nunmbers of choline eating microbes, are depriving choline an essential nutrient to their host.

Compared to mice that do not have choline-hungry microbes, choline-starved mice are susceptibie to metabolic diseases, give birth to pups with biochemically alterated brains, and moms as well as pups exhibit anxious behaviors. The study was published Aug. 24 in Cell Host & Microbe. UW-Madison Professor of Bacteriology, Daniel Amador-Noguez and researchers from Harvard University also contributed to the work.
'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.

Adequate Intake for choline

Choline Fact Sheet for Health Professionals, National Institutes of Health Office of Dietary Supplements

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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Aug 29, 2017   Fetal Timeline   Maternal Timeline   News   News Archive

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

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