Science AMA Series: I’m Kim Barrett, Professor of Medicine at the University of California, San Diego and Editor of The Journal of Physiology. This week, we published an issue on the microbiota, so I thought it would be a great opportunity to discuss how our microbes influence our wellbeing. AMA!

Abstract

Our bodies are inhabited by literally billions of microbes, with thousands of distinct species of bacteria, viruses, fungi and others that are referred to collectively as the microbiota. The most populous microbiota resides in our large intestine, but there are also significant microbiota in the airways, in the mouth, on the skin and in the female reproductive tract. Under normal circumstances, these microbes are harmless, and even considered beneficial to their host. They perform metabolic functions, educate the immune system, and protect us from infections with “bad” bacteria. Recent work, however, has suggested that when the composition of the microbiota is altered in specific ways, then the health of the site they colonize may be compromised.

For example, patients with inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis have a less diverse microbiota in their gut than healthy individuals. There is also increasing attention being paid to the ways in which other microbiota can influence the health of the sites in which they reside, and conversely, how the gut microbiota can influence the health of organs outside the digestive tract, including the brain. We are also learning how environmental factors, such as the diet and early-life use of antibiotics, can influence the make-up of the microbiota in either the short or long term and thus influence health status.

I’m eager to answer questions about any of these issues, and can also address how dangerous (pathogenic) food- and water-borne microorganisms, such as Salmonella and the bacteria that cause cholera, interact with the intestine to cause diarrheal disease. I’m also happy to answer general questions about biomedical publishing, including publication ethics and how new investigators can increase their chances that their papers will be accepted.

I will be back to answer your questions at 11:30 am ET, ask me anything!

On-line now and ready to start answering your questions! I'll get to as many as I can in the next two hours.

1.36pm ET: Wow - this was such an interesting experience but I am afraid I have run out of time and just can't get to all of these great questions. Thanks to everyone who participated by both asking and answering questions in this thread!

4.15pm ET: had a chance in my lunch break to add a few more comments.....thanks again to all and apologies to those whose questions I could not answer.

An overview of the current work linking gut microbes to depression symptoms would be very interesting. Specifically, is there any indication that specific foods can help encourage the population of microbes beneficial for mental health?

Thanks

kateasaur

At the current time, most of the evidence that gut microbes are linked to depression derive from animal studies (which is a limitation that applies to the field as a whole). There are correlative studies in humans, but Cryan and Dinan (major researchers in this particular subfield) concluded last year that a link between psychiatric symptoms and an altered microbiome needed more evidence, and the efficacy of targeting the microbiome for therapy was not yet proven (https://www.ncbi.nlm.nih.gov/pubmed/27005587). Nevertheless, the animal studies are intriguing, and this very active area of research will undoubtedly begin to pay off in the next few years. With respect to diet, fermentable carbohydrates and high fat have both been shown to alter the microbiome in a deleterious fashion, but these studies also have been conducted mostly in animals. or in GI rather than psychiatric disorders.


What is the best way to gauge the general health of you gut microbiota?

Similarly, what is the best way to increase the health of that group?

Lastly, if there is an event which hurts the overall health of the gut flora (I hope that's the right term???), say one has to use antibiotics, is there a best way, a quickest way, to return the mircobiota to its original, healthy condition?

JBHedgehog

Probably a straightforward (albeit indirect) method is to consider stool consistency and other abdominal symptoms. Research methods for monitoring the precise makeup of the microbiota are not yet widely available, though I do have some colleagues who routinely monitor their own stool microbiota and several companies will now analyze your poop for around $100. However there is controversy as to how accurate their results are (https://www.sciencenews.org/blog/gory-details/here%E2%80%99s-poop-getting-your-gut-microbiome-analyzed). As for methods to restore a healthy microbiota after an insult, many find that adding some probiotics or live yogurt to their diet for a period of time can offset the GI side effects of a course of antibiotics.


Could you elaborate on the effect anti-bacterial soaps have on our bodies? And how the upcoming ban of them (IIRC) in certain states will affect our systems as well?

Deray22

This question really relates to what has been called the "hygiene hypothesis", which holds that our ultra clean environment has disrupted our normal microbiota from early life, resulting in an immune system that has not been educated to respond appropriately. My colleagues Brett Finlay and Marie-Claire Arrieta have just published an excellent lay book, Let Them Eat Dirt, which addresses this issue in a very engaging and understandable way. Based on the evidence, banning anti-bacterial soaps for general use cannot be a bad thing (although we should not let up on infection control methods to avoid the transfer of pathogenic bacteria in hospitals, for example.


Two questions for you.

1) my daughter was born premature and given IV antibiotics at birth. What effect will this have on her microbiome?

2) I've read that the gut microbiome is different in children with autism. Any idea why that is?

slowlyslipping

Early antibiotics have been shown to impact the maturation of the microbiota, but the microbiota is also quite resilient so unless the treatment was unusually frequent or prolonged there may not have been a lasting effect. As for autism, we are still at the stage of developing correlations rather than having information about causality in humans. But it is very clear that there is a bidirectional communication between the gut and brain, and the microbiota is both a target and an initiator of that communication.


A 2008 study found that Small Intestine Bacterial Overgrowth (SIBO) was found in 46% of tested patients with rosacea, a chronic skin redness condition that affects millions and "has no cure". The bacteria reducing medicine Rifaximin was given to some of these SIBO positive patients, and 71% experienced clearing of their rosacea lesions.

As you mentioned that patients with IBD have a less diverse microbiota, are there things that patients with rosacea can try, or lifestyle changes they can make to fix the gut and hopefully improve the related disorders?

Why are treatments for these gut issues not more prevalent when there is much research to support that an unhealthy gut leads to so many problems?

Submersed

This is an excellent question. I think a lot has to do with people's general unwillingness to talk about anything that has to do with bowel functions, even to their doctors. I wasn't aware of the microbiota/rosacea link - fascinating! but the same applies here as for other conditions - a healthy, balanced, varied diet low in fat and processed carbohydrate may be of value, and a trial of probiotics is a possibility.


In your opinion, what is the best way to increase and preserve the diversity of gut microbiota?

hookers

Eat a well-balanced diet, including cultured/fermented foods, and avoid excessive fat and processed carbohydrates.


Question from a clinical standpoint: are there any macroscopic aspects of stool that correspond to it having a healthy diversity of microbiota? I.E. What does healthy-appearing stool look like in the toilet?

AthanasiusJam

Not too soft, not too hard!


Kim, could you discuss the role of intestinal microbes in producing serotonin, and how this "feel-good" hormone affects gut health? ( I understand that serotonin does not cross the blood-brain barrier, and serotonin in the brain is made in the brain. Help me understand serotonin in the gut. )

yogaman28734

Serotonin is a major controller of gut motility and sensation, and alterations in serotonin signaling have been documented in irritable bowel syndrome. The cells that make serotonin in the gut have been shown to express receptors for short chain fatty acids (SCFAs), which are major products of bacterial metabolism of undigested carbohydrates. Finally, some gut bacteria metabolize the serotonin precursoe, tryptophan, which in turn has implications for the production of appropriate gut levels of serotonin.


There's been plenty of talk and discussion about the gut microflora, but what about those living in other parts of the body? Such as, the nasal cavity and sinuses? Or under the fingernails? Do any traits that apply to the gut microbiome also apply to those elsewhere? How are they different?

S1erra7

Yes, this is a less appreciated area but rapidly growing area of study. I definitely would encourage you to look at our special issue of the Journal of Physiology, which has short reviews on the oral, skin and vaginal microbiota (http://physoc.onlinelibrary.wiley.com/hub/issue/10.1113/tjp.2017.595.issue-2/). Our external cavities all have their own distinctive microbiotas, but in aggregate they may encode many of the same sorts of metabolic capacities as seen in the gut. The specific populations may also depend on the type of environment - for example, the bugs on your forearm are different from those on your forehead. Lots more work to be done.


Thank you for taking the time to speak with us today.

How can we gauge our general level of microbiota health as individuals?

Do probiotics or Kombucha derive any benefit to our microbiota? If so how do we know which to use? Are there any signs to look for on labels?

FillsYourNiche

As replied to another post previously, there is not a simple way currently of knowing about our microbiota's composition, but general indices of gut health may give some clues. Likewise, finding effective probiotics may be a bit of a case of trial-and-error, but there is good epidemiological evidence for a beneficial effect of fermented foods like Kombucha.


Hi Kim, I'm a pharmacy student who will earn my PharmD this May. This has been hinted at by a few other questions, but not directly asked: what, if anything, is the role of early antibiotic use on future mental health (I.e. Frequent use of antibiotics in infants and children, and a possible association with depression, anxiety, etc... during teen and adult years.) Do you think something like fecal transplant may be used prophylactically in patients who require frequent antibiotics?

Thanks for your time!

radpotato

Early life antibiotics clearly disrupt the normal maturation of the gut microbiome, and have been shown to be associated with adverse outcomes in later life such as asthma and metabolic disease, presumably as a result of altered "instruction" of the mucosal immune system. Presumably that could extend to depression and anxiety as well, but I am not sure that has yet been proven in clinical studies. As for the prophylactic use of FMT, I'm not sure we are quite there yet, and my personal opinion is that FMT will evolve to the administration of key isolated species and/or their metabolites, but it's an intriguing idea. Somewhat akin to Rob Knight's recent work showing the value of inoculating newborns with the vaginal microbiome of their mothers if delivered by Caesarian section.


Do you think that in the future, when we understand more about how specific microbes and combinations of bacteria affect our body, that testing the microbiome and curating it with probiotics could be a standard part of a medical check-up? Or is it important for public health that each person have a slightly unique microbiome?

recentfish

I think we will move to a situation where the metabolic capacity of the microbiota can be tested and that this will be more important than the specific microbes that encode it. There could be many ways to arrive at this so I don't think there will be a wholesale effort to bring everyone to the same microbial profile. As for your second question, that is really intriguing. One could argue that diversity is always important, which is perhaps why we have multiple routes to arrive at the same metabolic capacity. Then, if you wipe out one type of bacteria inadvertently, you have redundant capacity for the same functions.


Sometimes, when I am constipated, I can perceive a certain taste and smell that arrives internally. Have direct nerve connections between the bowel and the brain been identified? What role to microbiota play in perception of satiety? What is the importance of the neurological phenomenon vs the blood chemistry in controlling weight gain or loss?

cosmotravella

Lots of nerve connections between the brain and gut, and gut nerve endings have been shown to sense bacterial metabolites. To the extent that the microbiota and their metabolites control the secretion of GI hormones, they clearly participate in satiety perception, but this still needs further study. And weight gain/loss is such a complex phenomenon, also encompassing societal and behavioral aspects, that the relative contributions of the factors you mention have not been worked out by any means.


I've heard a lot about problems related to damage to gut microbiota as a result of antibiotic usage. How much of a problem is this in the case of multiple rounds of antibiotics for a single condition, and what can be done to mitigate their potential negative impact?

Also, more broadly, can you expand on the issues related to the gut microbiome and antibiotic usage?

For reference, I have some formal biology background, part of the second degree I'm working on.

jddbeyondthesky

Particularly in early childhood, multiple rounds of antibiotic treatment are known to disrupt the normal maturation of the gut microbiota and its role in educating the immune system. To say nothing of the general problem of generating antibiotic resistance and super-pathogens. As we learn more about how to adjust the components of the microbiota via the diet and perhaps probiotic supplementation, we may have more tools to do something about this.


It seems that published studies are viewed at the end-all to their hypothesis but when investigating further you can see the studies lack statistical power and sample size. What is your opinion on the state of peer-reviews and fact-checking within the scientific community?

Whaty0urname

This is a huge issue that is getting a lot of attention at present. Clearly, peer review is not adequate in some journals, and there are too many investigators who do not understand statistics sufficiently to produce well-designed studies. Journals can help but increasing the rigor of their peer review and by developing guidelines for best practices in experimental design and reporting.


Can you give a brief sort of summary about species of bacteria and metabolites? Are we starting to lump bacteria into good and bad groups?(akkermansia, roseburia, etc) What are the hallmarks of "good" bacteria and their metabolites(scfa's?)? On what substrates do those bacteria feed? What about pathogenic bacteria? what do they like to eat and what do they produce? How does variable gut permeability play into all this?

bisteccafiorentina

Good and bad may be too simplistic. A "good" bacteria may be bad for you if in the wrong place. As for substrates and products, this is probably too big of a topic to tackle right now, but I would direct you to the work of Eugene Chang at the University of Chicago who has done a lot of work in this area. Gut permeability is also clearly important. We have done work to show that certain commensal and probiotic species can tighten the gut barrier so that pathogens and toxic metabolites are less able to penetrate and initiate inappropriate inflammatory reactions and a vicious cycle of further weakening of the gut barrier.


Strong evidence correlates aberrations in gut diversity with certain diseases. Phylogentitcally speaking, it seems to matter more that the microbiome is diverse and less important which species are specifically there. The hypothesis being that the gut microbial metabolome is relatively stable, regardless of specific species present. http://go.nature.com/2iQLOu1

Q1 - Have clinicians started to take the next step, looking at disease correlations with perturbation of the microbial metabolome?

Q2 - If so, what have they found? Do probiotics replace those missing metabolic pathways?

Prof--G

Absolutely agree with your comments about the metabolome. However, most of this work at present is still in preclinical models, although there has been a lot of attention to the way in which metabolic pathways change after bariatric surgery, for example.


Would you please share a little on the significance of skin flora? What might we do to improve or protect it?

ferry_quickly

The makeup of the skin flora depends on the characteristics of the skin site (moist, lipid-rich etc) but clearly has a role in immune regulation and protection against pathogens (e.g., acne-causing bacteria). Avoiding anti-microbial products for general use might be a good place to start to protect the populations.


When I was very young, I had a few instances of food poisoning visiting family in Mexico, I even contacted tuberculosis. I, of course, was given many antibiotics. I've had a lot of digestive issues since then, it was always a problem. I'm 36 now, and adopted a very low carb diet 3 years ago. During the initial transition, I had, to put it succinctly, severe dhiarrea. Like stuff was probably dieing off. And then, 4 months in, I had more energy, metal alertness, and general feeling of being present. And I no longer had crippling depression. From a completely anecdotal standpoint, I think that changing my diet also drastically changed my gut biome, and that, in turn, actually effected my brain function. It seems like what you're research has shown is that this isn't some woo-woo thinking, but an actual thing?

cata_tonic

Yes, an actual thing! You may also want to explore the evidence for so-called post-infectious irritable bowel syndrome, where an acute intestinal infection has long term effects on the nerves that sense distension and pain in the gut, resulting in pain, bloating, diarrhea and/or constipation. But I'm glad that you were able to stumble upon a dietary approach that works for you!


Hi Kim,

Being a female myself, I would definitely like to hear your input on the bacteria impacting female reproductive organs. Are the bacteria types similar or different than that found in the average person's gut? How does changing the bacteria population involved with the female reproductive organs affect fertility or menstruation? Lastly, do the bacteria in women's guts vary at all compare to men's, and is any bacteria involved with men's reproductive organs? (Or are girls just special)?

TL;DR give me the female-specific facts about the bacteria inside me!

Stupid_Rock

The vaginal microbiota is clearly distinct from that in the gut, although it is the source of the bacteria that initially colonize the gut of a newborn and may serve some of the same functions such as immune regulation. For men, presumably the only significant microbiota is that associated with the skin. You may want to check out Smith and Ravel's article in our special issue which discusses the potential effects of specific vaginal microbiota on reproductive physiology (http://onlinelibrary.wiley.com/doi/10.1113/JP271694/full)


How are studies coming along following those whom have had fecal transplants to treat CDiff? I hear good things, but it's usually the last in line after long lines of antibiotics have failed.

moes_tavern

Dramatic improvement in many cases, but you are correct that this is not yet the first line therapy (in part due to a lack of expertise and in part due to the ick factor on the part of both patients and docs).


What are your views on the genetic modification of gut bacteria in order to improve the health of people?

Is it even possible to create a sustained colony of genetically modified bacteria within the gut?

What are the potential problems, if possible, of doing so?

Following on from the synthetic cells AmA yesterday, do you see synthetic cells one day being used to treat patients with problems involving gut bacteria?

https://www.reddit.com/r/askscience/comments/5ohx4l/askscience_ama_series_hi_im_kate_adamala/

If so, how do you see this being applied?

thatsconelover

Proof of principle experiments with genetically modified bacteria have been reported but there would be significant regulatory burdens to overcome if such treatments are to enter clinical practice.


It's standard medical practice to test pregnant women for group B strep. Many carry the bacteria in the vagina and or rectum and it can have a negative effect on the baby when born vaginaly and exposed to the bacteria. As such these mothers are given an antibiotic drip during delivery. Further, the labia are doused with iodine typically. Should we rethink this method since these babies aren't starting out seeded as well with the mother's flora because of the antibiotics? Can we protect babies from group B strep and seed them with healthy vaginal flora as well?

Further, should cesarean section delivered babies be swabbed (eyes, nose, mouth, skin) with healthy vaginal flora upon being born?

sandbrah

Your points are precisely what my colleague Rob Knight recently studied. He showed that cesarean kids had a delayed development of their microbiota, and this could be corrected with inoculation with vaginal flora. It remains to be seen what this means for long term health/development, however.


I had read about some studies in which obese mice had received gut flora from lean mice and subsequently lost weight, and vice versa. Does this imply that a microbial treatment for obesity in humans could be developed, and if so, is there any interest in this?

Floomby

A lot of people are looking for just such a treatment!


Thank you for doing this AMA. I have a few questions.

Can you comment on gut flora transplants and their efficacy? I ha heard how fecal transplants can treat c. diff., etc. Are they possible to do at home? What are the best methods? Is it possible to completely CLEAR out or reset the gut biome and start over?

Is the gut biome hereditary in any way?

How do the gut flora biomes differ along the digestive tract? For instance, are there different bacteria in the large colon vs the small intestine? If so, do they perform different jobs, etc? And how does the body manage the biomes?

If my family has a new baby, what are the best ways to ensure that the most healthy possible gut bacteria develops naturally?

Also, lastly, are gut flora potentially both good and bad? Are there potential flora communities which can cause, say, autism or Asperger's, and are there ways to treat those communities or encourage the development of positive bacteria?

Sorry for all the questions, but, you've chosen a fascinating field!

catsfive

I do not recommend do-it-yourself fecal transplants. Too many risks if the stool you are using has not been confirmed to be free of pathogens.


Do you have any knowledge about the connection between gut bacteria and Parkinson's Disease? If I recall correctly, research is only beginning on this topic, but I've heard about it a few times and was wondering if you had any input.

yogace

the human studies thus far are only correlative, but this is an interesting and important area of research that should yield insights in the near future.


Greetings Professor, and thank you for your time. I have already seen someone ask you about Kombucha as a possible additive to benefit ones internal micro organisms. I would like to know, about Kefir milk.

Does Kefir have a beneficial purpose in boosting the good bacteria within our bodies? (ie Probiotioc)

Thank you.

JoseMustardSeed

Yes, along with other related foods.


Completely ignorant starting point: how do you go about classifying and cataloging what seems like an enormously complex data set? Are the bacteria, by and large, already identified and now it's "just" a matter of identifying and cataloging them within a host? Or are we discovering whole new categories of bacteria?

I guess the point is: where are you starting?

Zinjifrah

This was a big sticking point in the field initially since many of the bacteria cannot be cultured. Now they are identified by sequencing. The estimate is that healthy individuals harbor at least 1000 different species. Not to mention viruses, fungi, protea....we're just getting started, and as you imply, the bioinformatics challenges are huge.


I've heard with probiotic supplements, it isn't the number of cultures but the number of different types of cultures. Is there any truth to this?

chrisbar1104

There's quite a bit of evidence that mixtures of different bacteria are more effective than single bacteria. Perhaps they have complementary metabolic functions, or mutually help each other to colonize the gut.


Professor, has your research formed links that healthy microbiota may help alleviate other types of auto-immune disease? Besides Crohn's.

bazooka_matt

Others are exploring a role in asthma.


Twenty years ago my "crazy" grandmother started lecturing all of us about the importance of gut bacteria and the dangers of antibiotics. When my grandfather got sick and the hospital gave him antibiotics she fed him yogurt. She died a few years ago. How long has this research been out there??

OolasBF

People have been promoting the health effects of yogurt for perhaps 100 years. Bu it has only been in recent years that we have been able to actually characterize the bacteria that are present with molecular tools.


Hello, I recently took an interest in the microbiota. My question to you is: how (if at all) do you see the microbiota changing the overall approach to future in vivo experiments?

ponchoskunk420

We'll have to be a lot more careful about co-housing groups of mice with different genotypes so we can be sure that effects seen are due to genetic differences and not the fact that mice in different cages may have distinct microbiota.


I have a friend who acquired an oral allergy reaction to peanuts via her boyfriend. Any idea how the allergy might have been transmitted? The symptoms she now exhibits is her tongue and throat swell up upon exposure to peanuts.

fatalist23

Allergies are not transmissible. There must be something else at play here.


Does microbiota vary from geographic region to geographic region?

libmaven

Yes


I'm semi lactose intolerant (fart bombs). Does this come from a microbe related issue? I love milk, ice cream, cheese, and alot of other food. Im just curious

eheheh123

More likely a result of not having enough of your own lactase enzyme that breaks down lactose. Very common in certain ethnic groups and happens to all of us to some extent as dairy products become a less important part of our diet.


Would we survive if all bacteria died?

vinegary

Germ free animals survive, but their immune systems are rudimentary and they have other problems. Some vitamins require bacterial metabolism too. so in the real world, we are probably dependent on our microbes.


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