I’m live tweeting the Harvard Probiotics Conference...starting a new thread for the afternoon session. First speaker also has the Best Hair among Celiac Disease Researchers, Alessio Fasano MD
Here’s the link for this morning’s thread
Celia disease is the only autoimmune disease for which we know the trigger. 
No one really knows the cause of the increasing prevalence of Celiac disease...they used data from retrospective studies in a 10 year prospective study and found nothing except nonsignificant trend with GI infection in first year of life.
Dr Fasano is also saying the field of the microbiome is shifting from structure to function. Describing the microbiome is not nearly as useful as describing and understanding the functional components of the microbiome.
Nutrition has the biggest impact on the microbiome of anything (you’re only born by c section once, you take antibiotics a few times...you eat multiple times a day obvs)
Fasano also agrees that mouse models are crap...especially when we are talking about the huge structural components of microbiome (plus mice eat their poop and we don’t)
To that end they are starting enormous prospective studies of children in Europe and US and they have to use AI to manage the huge amounts of data.
Metagenomics is the study of the metabolic functions of the microbiome. They have designed human gut “organoids” (ie a human gut in a lab) to study microbiome in lieu of animal models.
Once we get this data we can figure out cause/effect and develop functional metabolite targets.
Gettin’ full hygiene hypothesis here ahhhhhhhhh
(These are Dr Allan Walker’s slides with the original colors and fonts of the first iteration of PowerPoint. Respect!)
Case in point:
Next up is Gary Wu MD from UPenn on diet and microbiota during adulthood in health and disease
There’s a bidirectional relationship between bacteria and bile acids. Primary bile acids are made into secondary bile acids by bacteria. Bile acids are also toxic to bacteria (G+ more than G- like enterobacteria)
The enzymes that transform primary to secondary bile acids are only found in the bacteria in mammalian guts. Bile acid modifiers are already used to treat primary sclerosing cholangitis and NAFLD.
Wu going through the trillion data points you have to work through to try to understand these bile acid/bacterial interactions and shows how administering bile acids changes the composition and metabolism of the microbiome.
Probiotics have little impact on the fecal microbiota in humans, but probiotics may have a big effect in the small bowel and the transcription and metabolic processes in the small bowel (much harder to study what’s going on in small bowel as opposed to getting a stool sample)
Bile acid detection are two orders of magnitude lower in the stool as in the small bowel.
All these microbiome researchers are big proponents of fiber and are frustrated by mouse models lol.
Inflammatory bowel disease (crohns, UC) started increasing a century ago in developed world and is increasing in developing world. Always associated with dysbiosis.
Treating dysbiosis can help IBD
They use gross nasogastric tube diets to control crohn’s disease in many countries. It works, but they don’t know why (excluding some toxic elements of western diets?)
They are finally starting to do the emulsifier and artificial sweetener studies that torched the mouse microbiota in humans.
More studies of the metabolites of the microbiota and their associations with human disease...(function, function, function) again, composition of microbiota less important than the metabolites.
Also doing studies of Vegans, omnivores, and people on elemental treatment diets in healthy people and those with crohns...correlating with microbiome and metagenomics. It’s...complicated.
Vegan and omnivore microbiome bounce back pretty quickly (within days) after antibiotic treatment...the microbiome on a elemental treatment diet 4 crohns doesn’t bounce back. That means you can completely reformulate microbiome with a (gross) diet. (These were all healthy folks)
They are trying to find safe whole foods that could be a diet treatment for crohns or UC that’s not elemental tube feed (it’s tube feed because it is literally too disgusting/unpalatable to eat).
Wu thinks diet alone could work in selected individuals and others could use a combination of diet and less aggressive immunosuppressive regimens than we use now.
Next: Erwin G. Zoetendal PhD also from the Netherlands. “Intestinal Microbiota in Developed vs. Developing Countries” (he brings up this study psychologytoday.com/us/blog/evolut… )
Proteobacteria are associated with poor health in Western world, but levels are high in the Hazda, suggesting (again) that what *is* good and bad with the microbiota is not necessarily what is *associated* with the good and bad in the microbiota...
So green are rural Dutch and red urban Dutch...that’s a heck of a plot
Here’s another interesting twist...seasonal changes of microbiome plots in the Hazda (one test in time won’t work in a population with seasonal changes in diet)
I love this guy...there’s a paper showing that the egg came before the chicken 😂
Here’s that first study by this guy I mentioned above, where they switched diets between Africans and African Americans for 2 weeks. Here are the changes in the metabolic products of the microbiome in just two weeks (the African diet had huge amounts of fiber)
The actual composition of the microbiome didn’t change much with the diet intervention. The function, however, was profoundly changed.
Anyway, that’s it until tomorrow!
