Delighted to share this perspective piece by Lewis Yu on microbial regulation of serotonin and neuroimmune interactions. Looking forward to sharing more on this topic soon 🤞

RT @Hypothesisfund: 5/5 Awardee @zhang_chuchu explores how different body states (like pregnancy) may change what neurons sense & how they….

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Happy to be able to present this work by Elena & co, now up in final form: It now has insights on how maternal consumption of a low protein diet during the pregnancy leads to lasting effects on maternal milk and immune status during the postpartum period.

Overall, this was an exciting proof of concept showing that i) a gut bacterium can be used to offset environmental risk for neurotoxicity and ii) bacterial treatment of pregnant mice has the capacity to protect the brains of their fetuses.

To see if it reduces methylmercury to levels that are biologically meaningful, we tested it in pregnant mice. The bacterium reduced methylmercury bioaccumulation in maternal & fetal tissues, including brain, & reduced signs of toxicity in fetal brains from dams fed tuna or salmon

To put it to the real test, Amina got a bluefin tuna from a fish market & processed it into a fine powder. The bacterium reduced fish methylmercury when in culture & when monocolonized in mice that were fed fish-based chow. It even worked by oral gavage to conventional mice!

Kristie engineered the gut bacterium B. thetaiotaomicron to express enzymes that reduce methylmercury into forms that are less toxic & easily excreted, and showed the bacterium quickly reduces methylmercury in culture & in the guts of mice orally gavaged with methylmercury

This made us wonder, if certain soil microbes survive by detoxifying methylmercury from their environment, could we use a microbe to detoxify methylmercury that enters the gut environment from eating mercury-containing fish?

We were inspired by work by Fatimawali, Kepel, and Tallei at Sam Ratulangi University that found mercury-resistant soil bacteria from a polluted gold mine.

We learned from Amina’s foundational research that levels of the neurotoxicant methylmercury are rising in fish, which poses a major issue for the billions of people iwho rely on fish as a major source of nutrition.

This all began with a chance meeting at Scialog by @RCSA1—think science speed-dating with rapid seed funding- a fun & impactful way to advance new ideas. Thanks to @RCSA1 for supporting collaborative, interdisciplinary research & making this possible!

Thrilled to share this collaborative work by Kristie Yu, Francis Chandra, Amina Schartup and teams @Scripps_Ocean and @UCLA showing that an engineered gut bacterium can reduce the neurotoxic effects of dietary methylmercury

RT @LinChangMD: 🙌Grateful and excited about the Wang’s visionary and transformative $25M gift! The UCLA Walter and Shirley Wang Center for….

RT @LinChangMD: Congratulations, @AndreaShin_GI! So happy and proud of you!.

RT @stephorch: Curious about how the gut microbiome modulates the neurological health of pregnant women and their offspring? Check out my r….

Huge thanks to Kelly Jameson who fearlessly led this study (& overcame the many technical hurdles of doing so!) together with invaluable guidance from Felix Schweizer! Also to Sabeen Kazmi, Taka Ohara, @CelineSon11, Kristie Yu & colleagues for helping to make it possible.

Overall, this work adds key details to existing work on how microbes & their metabolites interact with vagal neurons. It shows that they can do so when applied to the lumen of the small intestine & when considering the specific subsets of metabolites that come from the microbiome

By stacking stimuli for in vivo calcium imaging, the SCFAs, BAs, and 3-IS seemed to activate some distinct subsets of vagal neurons, with some acting faster vs. slower than others.

Perfusing select SCFAs, bile acids & 3-indoxyl sulfate into the SI increased vagal activity & activated NTS neurons. This was prevented by particular receptor antagonists, which together with in vitro screening, suggested that they act indirectly via enteroendocrine cells

To find out which magic molecules from the microbiome may be responsible, Kelly subjected small intestinal vs. cecal contents from mice with different microbiomes to metabolomic profiling and screened the top candidates for their ability to increase vagal activity.