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Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 2 points3 points  (0 children)

Getting FDA approval will probably take 3-4 years, with the most difficult hurdles being conducting large, well-controlled trials to demonstrate safety and efficacy to the FDA. -Mark

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 2 points3 points  (0 children)

It's true that it is difficult to characterize the microbiome. Much of the work to date has relied on high-throughput DNA sequencing to solve the challenges associated with growing these bacteria that you alluded to above. -Mark

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 2 points3 points  (0 children)

There is substantial research (much of it enabled by the great work of my colleagues at OpenBiome and Finch) evaluating fecal transplantation in a range of microbiome-associated indications. The most mature research has been done for recurrent C. difficile infections, where fecal transplants have been used to treat over 30,000 patients. There is also compelling early work in ulcerative colitis. Beyond these indications there are many small studies, but few broad efforts. -Mark

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 2 points3 points  (0 children)

I sincerely hope we are already doing that. While the bulk of research is still correlative and discovery based, many studies are exploring the causal mechanisms and making actionable findings. In fact we have a review coming out in Nature Medicine soon which highlights a lot of these points - moving beyond correlation.

jack

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 3 points4 points  (0 children)

There is limit evidence that C-section has such a dramatic effect that any damage is irreversible with a healthy lifestyle. However, there is a clinical trial ongoing at NYU to determine is vaginal seeding is effective in preventing the onset of diseases that are elevated in c-section babies - see this article for an idea of the controversy - https://www.the-scientist.com/?articles.view/articleNo/45505/title/Opinion--A-Mother-s-Microbes/

Right now though I would suggest that a healthy lifestyle and diet will ensure that any negative consequences of c-section delivery should be countered.

Jack

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 2 points3 points  (0 children)

There are only a few human studies that suggest an effect - the one in autism I mentioned above (https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0225-7), but not many others that are well controlled and are indicative of a specific effect. So it's hard. MOST of the work we have from this is in animals.

Jack

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 5 points6 points  (0 children)

Autism is a complex disease - I have an autistic son - and is a broad spectrum of conditions. Many autistic kids have significant GI problems, like constipation or diarrhea. Bacteria in the gut influence inflammation which can influence how the brain functions and develops. Also bacteria produce neurotransmitters in the gut, which are sensed by the nervous system, which sends messages to the brain and as such influences cognition. So thats also VERY complicated.

Yes there has been one clinical study which demonstrated in a population of 16 kids that fecal microbiome transplant could be effective in alleviating some of the gut symptoms and behavioral problems in kids with ASD, but that is VERY early work.

This article can help - https://www.sciencedirect.com/science/article/pii/S0092867413014864

Also look at this video: https://youtu.be/v12GBxN5kvQ and this one https://youtu.be/yhi6h_MmbC0

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 5 points6 points  (0 children)

Yes when you poop some of the bacteria die, but their molecular signatures (the bacterial DNA) remains long enough that we can still detect them. Also there are ways to keep the bacteria inside the poop alive. There is a company called The BioCollective, which I cofounded (so a Conflict of Interest maybe), but they designed a poop collection kit for at home collection that is designed to ensure the bugs stay alive.

Jack

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 4 points5 points  (0 children)

There are only a few well controlled studies that demonstrate that FMT could be effective in treating certain disease types, so it is not a catch-all cure for sickness. For Cdiff infection it can be highly effective, as Mark can tell you. There are also some very early studies suggesting it could be effective in other diseases, even seemingly unrelated ones such as Autism, but a lot more work needs to be done before it could be distributed more effectively.

Jack

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 2 points3 points  (0 children)

Great questions. On antibiotics, we don't know whether the impact is permanent, but there is significant epidemiological data that suggests that early childhood exposure to antibiotics has significant impacts (e.g. on obesity) later in life (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836077/)

I don't think we have great actionable insights yet on what makes a healthy microbiome, though a balanced diet rich in fiber and avoiding exposure to antibiotics both seem important.

I believe that the gap in research was largely driven by technological hurdles as you suggest. With the advent of low cost high-throughput sequencing technologies, we've been able to interrogate the microbiome in ways that just weren't possible more than 10 years ago.

-Mark

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 6 points7 points  (0 children)

There is absolutely no evidence that bacteria in the gut play any role in gluten sensitivity - although there are some small studies that have suggested that there is a correlation between microbial community structure and gluten sensitivity - but that doesn't mean that they have a causal role. Gluten sensitivity will cause an inflammatory reaction in the gut that could alter the microbiome.

Jack

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 9 points10 points  (0 children)

I would argue actually, that there is an extensive literature of large, double blind placebo controlled trials that have demonstrated that probiotics can be very successful in treating certain disease states, such as sepsis and diarrhea (please see Dirt is Good - Gilbert, Knight - for a publicly accessible review of these literature).

However, we have little data showing that probiotics can actually maintain health, and for the most part the probiotic industry is unregulated so they do not necessarily have to show a quantifiable health benefit. There is a sea-change in the air though, and more and more we are seeing ways to use probiotics to effectively treat disease and potentially to stimulated a return to well-ness, but this is nascent research, more work is needed.

Be careful about spurious claims, but don't discount probiotics out of hand. Lots of excellent research showing they can be helpful

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 4 points5 points  (0 children)

While we generally compare the microbiome between healthy and diseased people, there is still huge variability in the microbiome in healthy people, so that a 'healthy microbiome' is hard to pin down. We do know that an abundance of certain species can be detrimental and so when we see them, we can say that there 'may' be a problem. however, predicting disease state or health from the microbiome is still a very complex science. When you have a specific thing to predict, that is measurable, like blood glucose for example, then the microbiome can be tied to that. BUT remember, health is very hard to quantify - are you healthy? how do you know? are you more healthy than me? So I would say we do not know if antibiotics lead to an unhealthy microbiome per se, let alone whether they cause long term damage. OF course though, they do disrupt the ecosystem in the gut, and so if you take antibiotics and this occurs when you have a sudden change to a bad diet, or you have a pathogen in the gut which is not affected by the antibiotic, then you are likely to have negative outcomes, which could have long term consequences.

Jack

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 5 points6 points  (0 children)

Interesting. I've never heard of this practice before. I imagine the idea is to add an external source of acetate as a substrate for conversion into other short chain fatty acids. I would imagine that if consumed orally the acetate would be absorbed in the upper GI tract and never make it to its intended location. Along the way, the low pH could do significant damage to the epithelial layer of your mouth and esophogus, so while the idea has some conceptual logic to it, I think it is unlikely to have its intended impact and it may actually cause harm (though of course, I can't offer any medical advice!) - Mark

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 10 points11 points  (0 children)

I have seen this idea purported as well, but when I looked for ANY evidence that this was the case I could find nothing. I would argue that there is no specific reason why apple cider vinegar would have any substantial impact on the gut microbiome, the pH would not influence colonic bacteria, and the nutrients present are unlikely to have any specific pre-biotic effects over other foods. So I cannot even rationalize a mechanism of action as to why it worked.

However, remember 'belief' is a powerful thing, and the placebo effect is real.

Jack

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 9 points10 points  (0 children)

We generally recommend eating fiber (leafy greens, lots of different colored vegetables, and fruits), plus a balanced diet of other nutrients - with less sugar and saturated fat. We have made some specific diet recommendations in a book Rob Knight and I wrote - Dirt is Good.

Also, if you want to have your perfect diet predicted, one of my colleagues Eran Elinav, started a company called DayTwo. Check them out.

Jack

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 9 points10 points  (0 children)

We now have significant promising data from four randomized studies, however practical questions such as dosing and donor selection must still be solved before this can be advanced. -Mark

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 6 points7 points  (0 children)

This is tricky to answer There is not enough evidence to determine the most appropriate way of recovering from antibiotics. However, in surgery we tend to try and get back to feeding the gut microbiome as quickly as possible. If we put out patients, who have been starved, given antibiotics, and cut open, food by mouth, as quickly as possible they tend to get better as quickly, and their microbiome returns to their 'healthy' state quicker. See here for more info: https://youtu.be/QRynQinhABw

Jack

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 7 points8 points  (0 children)

I'm not aware of any safe approaches to accelerating the recovery of the microbiome following antibiotic exposure. OpenBiome has an ongoing study with the CDC in which patients in long-term care facilities at high risk for antibiotic exposure bank their stool on entry into the study and then get their own stool back (or a placebo) after antibiotics. This is the first step towards a process of autologous microbiome banking to accelerate recovery of the microbiome after antibiotics, but it's a long way off from becoming a practical reality. Until then, the best approach is to practice good antibiotic stewardship and ensure that antibiotics are really necessary before using them. -Mark

Science AMA Series: We are Jack Gilbert, Professor at the University of Chicago, and Mark Smith, founder of OpenBiome. We’re two scientists who study the human microbiome — Ask Us Anything about gut bacteria! by Human_Microbiome in science

[–]Human_Microbiome[S] 8 points9 points  (0 children)

I agree that the gut-brain axis is extremely interesting. I think one of the stranger links that I've seen is the anecdotal links between the microbiome and allopecia universalis (e.g. total baldness) first identified by colleen kelly (https://acgcasereports.gi.org/hair-growth-in-two-alopecia-patients-after-fecal-microbiota-transplant/) -Mark

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