Hi! Luca, Ryszard, and Dr. Ryan Martin are back to answer all your microbiome and gut health questions. About two years ago we decided there was a need to improve the way digestive health conditions are diagnosed, monitored, and treated. We're a group of patients, doctors, and researchers dedicated to the goal of helping people trust their guts again.

We're here to share knowledge on the gut microbiome, artificial intelligence for medicine, bioinformatics, Phyla (our startup), and more.

Our last AMA was more popular than we could have ever imagined with over 600 questions during our last AMA. So we're back to answer anything we might have missed :) Time for round 3....ask us anything!

Phyla social media: Instagram LinkedIn Twitter

Feel free to send me a message on Twitter or check Phyla's website for more!


EDIT: Thanks for all your amazing questions! We want this to be as informative as we can, so if there are any topics you think we missed and would like to see in the future, send us a message on twitter! We had a great time :)

Comments: 528 • Responses: 23  • Date: 

VS-Banana231 karma

What's the research looking like for the connection between gut microbiome health and prevalence of psychological conditions like depression?

cucciaman245 karma

Hey u/VS-Banana & u/LordFluffy! I always love discussing this topic! The research on microbiome and mental health is ongoing and never fails to fascinate me. The brain-gut axis is a two-way relationship and these two organ systems basically communicate with each other through signals, the microbiome, and the vagus nerve. Here's an example of this research. The brain-gut axis is linked to both microbiome and mood disorders.

For example, mood-related disorders like anxiety and depression have been linked to abnormal gut microbiome activity, such as stress responses and inflammation occurring due to compounds produced by gut microbiota (for example, short-chain fatty acids and serotonin). The risk of such mood disorders is also increased in people with gut issues, such as inflammatory bowel disease and irritable bowel syndrome, due to changes in healthy gut bacteria and the stress of coping with chronic, stigmatized gut health issues, among numerous other factors. In fact, this study suggests that people with IBS are three times more likely to have anxiety or depression, so that's not a link we can really ignore if we want to investigate the relationship between the brain and gut.

So gut microbiota trigger stress responses that affect mood, while being stressed or anxious can also trigger gastrointestinal symptoms. It makes sense why many people with gut issues are encouraged to try meditation; healing and centering the mind and body can help relieve symptoms (including anxiety, abdominal pain, etc)! This helps to explain why we consider the relationship between the brain and the gut bidirectional. You can read more on the science here!

Best, -LC

sdnw88226 karma

Are probiotics in pill form beneficial, or just a waste of money? What would you suggest is the best strategy for achieving "optimal" gut health?

cucciaman225 karma

Hi /u/sdnw88!
To start with, at this point no probiotics have been approved for the treatment of any disease. But this doesn’t mean they do not have the potential to help in the future. Several clinical trials have been completed to determine if probiotics have an effect on a variety of different health measures. One exciting probiotic in development is VSL no. 3 which consists of 8 different probiotic bacteria. Some small clinical trials have suggested this probiotic helps prevent pouchitis in adult patients, although further larger studies are needed to better assess the probiotics efficacy (https://pubmed.ncbi.nlm.nih.gov/17033538/).
One aspect that makes developing a probiotic difficult is the personalized nature of the microbiome. The gut microbiomes of two individuals can vary drastically depending on a variety of lifestyle factors, with these differences affecting whether the probiotic bacteria will be able to thrive in their gut. In future studies, it will be important to identify the bacteria in the patient’s gut before and after probiotic treatment to better understand the dynamic changes occurring and hopefully identify you will be responsive to the probiotic.
As I’ve mentioned elsewhere, one of the best ways to maintain a healthy gut is through the food you consume. Your diet not only provides the nutrients you require but also those that the bacteria in your gut need to survive. One dietary pattern that provides a rich source of nutrients for you and your gut is the Mediterranean diet, which is rich in fruits, vegetables, nuts, legumes, olive oil, and meats such as fish and poultry and limits consumption of red meats and refined grains.

elbers109 karma

How far are we from widespread poop transplants?

cucciaman99 karma

Hi u/elbers, great question! Fecal microbiota transplantation (FMT) has a lot of potential as a treatment for microbiota-mediated diseases, but the research is still in its infancy. The only approved indication for FMT is currently relapsing C. difficile infection. Use of this treatment for other illnesses has only been in clinical trials.

There's lots of unanswered question about FMT, like what dosages work best, what makes the ideal donor, what kind of diet works best after a transplant, should FMT be done once or in a higher frequency, etc. This takes years of research, not to mention investigations of the long-term efficacy of this treatment, how regulatory measures can be determined, and what to do to standardize research protocols so that scientists, doctors, and other health professionals can assess the research on FMT for different purposes on an even playing field.

So although FMT is gradually emerging as a possible option for Crohn's, colitis, cancer treatment protocols, and more, we are still a while away from having all the answers we need in order to make this option more widespread and accessible to different people and communities. I assure you there are plenty of people working on this though! Hope that answers your question! -LC

Nikonegroid78 karma

I'm of the belief that I should eat as many variety of foods as possible to increase my gut biome. Am I right in this line of thinking?

Also, does alcohol and spicy food kill gut bacteria?

cucciaman104 karma

I'm of the belief that I should eat as many variety of foods as possible to increase my gut biome. Am I right in this line of thinking?

Also, does alcohol and spicy food kill gut bacteria?

Hey /u/Nikonegroid!

Great question, you are definitely correct. Diet diversity is closely linked to microbiome diversity which is linked to overall health. However, it is important to mention that dietary diversity alone will not improve your microbiome diversity unless the dietary quality is also high. For example eating 10 different kinds of junk food will not improve your diversity, while eating 10 different kinds of vegetables will.

Alcohol in general has a tendency to kill beneficial bacteria, especially in the oral microbiome. This then predisposes to the colonization by pathogenic bacteria and further problems.

Spicy food on the other hand also has an impact on the microbiome, as shown in a few studies, but whether this is directly beneficial to our health still requires more research.


DungeonMaster2450 karma

So, I've heard that the gut biome can have a great affect on a person's overall health. Could you give examples of that, and how can we improve and ensure our gut biome is optimal?

cucciaman70 karma

Hi /u/DungeonMaster24!
That is a great question!
There are several links between your gut microbiome and different diseases and your overall health. For example, the gut microbiome of patients with inflammatory bowel disease is drastically altered from healthy individuals. Two consequences of the altered gut microbiome are: Individuals with IBD have a different collection of bacteria in their gut which can promote inflammation and the bacteria produce different compounds which are absorbed by the gut and can have adverse effects on the individual.
In addition to links with diseases, the microbiome has also been associated with a person’s quality of sleep and exercise levels. For example, the bacteria Blautia was associated with a negative effect on sleep quality and the bacteria Veillonella was associated with endurance athletic performance.
One of the most important ways to maintain a healthy gut microbiome is through the food you consume. Your diet not only provides you energy and nutrients, but also feeds the bacteria living throughout your gastrointestinal tract. One dietary pattern that provides a rich source of nutrients for you and your gut is the Mediterranean diet, which is rich in fruits, vegetables, nuts, legumes, olive oil, and meats such as fish and poultry and limits consumption of red meats and refined grains.

Grateful_Undead_6949 karma

Are we even close to finding a cause or cure for UC? Biologics have helped me a bit but I still have symptoms. It would be easier to accept if I knew why I ended up like this and if there's any hope for the future

cucciaman48 karma

Are we even close to finding a cause or cure for UC? Biologics have helped me a bit but I still have symptoms. It would be easier to accept if I knew why I ended up like this and if there's any hope for the future

Hey /u/Grateful_Undead_69 and /u/ClyffCH,

IBD-type illnesses such as Crohn's disease or Ulcerative colitis (UC) are complicated to treat as they are highly personalized and multifactorial. Indeed, like other autoimmune diseases, they are a result of a fundamental shift in how our entire body operates and an actual cure is still distant until we understand how to fully revert such a shift. In the meantime, there are already treatments such as the biologics you mentioned that can mostly eliminate disease symptoms, as well as new drugs being researched and developed.

In general, there are 3 components to an illness like UC. The immune system, the microbiome and the external environment (lifestyle, stress, diet, etc.). Most but not all medications given by a GI doctor will impact the first component, which is the immune system, and I am happy to hear that biologics have helped you even if only somewhat.Aside from biologics, you can try to address the other contributors to the illness. Diet and lifestyle can play a large component in UC. Indeed, many patients find relief from symptoms by applying dietary changes. Unfortunately, yet again, this is highly personalized. One diet may work for someone else with UC but it might not necessarily work for you. Similarly, other patients find that their largest trigger may be stress and find the most relief by using anti-depressants or other ways to address their mental health.

To help discover what could be a potential trigger for the UC, many patients benefit from keeping a log of their diet and lifestyle to determine which factors actually contribute to their symptoms so that they can exclude them. I am actually working with a team of doctors, data scientists and IBD patients on an app that allows patients to track their symptoms and lifestyle in order to quickly discover triggers and help them manage their illness.

I hope this was helpful and wish you the best in managing your UC.


ThongofSekhmet39 karma

Do artificial sweeteners have any effect on the gut microbiome?

cucciaman80 karma

Hey /u/ThongofSekhmet!

This is a very interesting topic. In general, sweeteners do have an impact on the gut microbiome, and specifically artificial sweeteners have been shown to change the composition of the gut bacteria and impact glucose intolerance. Further research in humans demonstrates that the glucose intolerance seen during extended use of artificial sweeteners such as saccharin could cause a gut microbiome shift, causing glucose intolerance.

Extended use of certain artificial sweeteners does indeed have an impact on the microbiome and it is thought that extended use of them could lead to pre-diabetic/glucose intolerant states.



Ashgardian36 karma

What exactly is a "leaky gut?" I've heard this term tossed around quite a bit (especially after receiving a lupus diagnosis). Is leaky gut widely recognized by physicians? Does leaky gut have anything to do with autoimmune disease? I'd appreciate any insight into this new-to-me concept as a potential path to healing inflammation and feeling better.

cucciaman25 karma

Hi u/Ashgardian! Leaky gut is means that the intestinal lining has essentially been compromised. The intestinal wall (or epithelium) is a strong but thin, single-cell layer that separates what's inside the digestive tract, including food particles and microorganisms, separate from the rest of the body. This layer can become porous, most likely due to an imbalance in the gut microbiome (intestinal dysbiosis) that can damage the gut wall. This means that the intestines can be penetrated and compromised more easily, which can expose the immune system 'around' the intestines to be exposed to triggers such as bacteria and dietary elements. This leads to more immune system activation, damaged intestinal tissue, and inflammation. All of this can affect immune reactivity such that autoimmune disease can occur, but a lot of other factors are also involved, such as genetic susceptibility and environment. More info here. Some research even considers leaky gut to be "a danger signal for autoimmune diseases", and that improving gut microbiome health can modify how permeable or porous the intestine is in order to help those susceptible to autoimmune disease. Hope that makes sense!

As for physician recognition of leaky gut, it can really vary. There are many doctors who don't investigate microbiome health enough, or even consider issues like IBS and leaky gut, but there are also many doctors that have an integrated approach to care and will consider these issues with knowledge and seriousness!

Best, -LC

CurrentEmu24 karma

Docs say once flora is gone, it’s gone but if the appendix is a reserve, it should be possible to restore the microbiome. Or is it not? What’s the best way to restore the microbiome after antibiotic damage? Are spore probiotics a good choice?

cucciaman26 karma

Interesting question! I'll admit that I haven't investigated the role of the appendix as much, but there's certainly some research on it. For instance, when the vermiform appendix (part of the digestive tract lying by the end of the small intestine) is removed, or even the gallbladder which is another important aspect of the digestive system, an unhealthy shift in the diversity and composition of the gut microbiome has been found (check out the study). This suggests the importance of the appendix in sustaining microbiome health. While the appendix may contribute to the growth of good gut bacteria, much of the focus for restoring the microbiome remains on diet (tons of fiber-filled foods), supplementation, enough exercise and sleep, and even fecal transplants when possible.

Restoring gut microorganisms after the effects of antibiotics can be tricky, and many times probiotics are recommended. Fermented foods contain a lot of probiotics, which can help good bacteria propagate and thrive. A recent study looked more closely at how fermented foods, such as yogurt and kombucha affect the gut microbiome. Fermented foods increased the diversity of bacteria found in the gut... however, few of these bacteria were actually from the fermented foods in the people’s diets! The researchers suggested it was because of the other components of the fermented foods, for instance byproducts of fermentation that help new bacteria thrive. The study: https://pubmed.ncbi.nlm.nih.gov/34256014/ .

Of note, as is the case with most probiotics out there, only a small amount of the beneficial bacteria can actually make it all the way to our intestines and survive. While many people personally have said they feel better after consuming probiotic supplements, the truth is there's not enough medical or scientific evidence out there yet for us to stand behind it 100%. There are so many strains of bacteria that some patients may not even be taking in what their gut is missing or needs. So this is an area of research that needs lot more time to develop and advance; in the meantime, we certainly vouch for a well-rounded diet with tons of whole foods! -LC

LordFluffy22 karma

Have you found any correlation between gut health and worsened anxiety (as opposed to anxiety causing gut problems)?

cucciaman10 karma

Hi u/LordFluffy! Please check my response to your question in the previous post on microbiome health and psychological disorders!

cornucopiaofdoom18 karma

Does using a proton pump inhibitor affect the gut biome? My IBS-D symptoms went away after starting on a PPI but was curious as to why this would be the case.

cucciaman20 karma

Does using a proton pump inhibitor affect the gut biome? My IBS-D symptoms went away after starting on a PPI but was curious as to why this would be the case.

Hey /u/cornucopiaofdoom,

Great question. The use of PPIs has a large impact on the microbiome, with some studies saying they have as much of an impact as antibiotics. Some studies have also shown that PPIs can help improve IBS symptoms, but only in a percentage of people. On the other hand, PPIs have been also shown to worsen or trigger IBS because they may help with the colonization of the gut by bad bacteria.

Indeed, it seems to be quite personalized and more research would be required to fully understand this relationship. In your particular case, it is possible that your particular microbiome benefited from the effects of PPIs, allowing for your IBS-D to resolve. It is also possible that another factor occurring at the same time as you taking your PPI helped your IBS-D resolve.

I hope this gives you some information.

Cheers! RK

KaneHau16 karma

I have extreme lactose intolerance, which extends to just about all the makeup of milk. This extends to beef, beets, and many fermented foods.

I'm middle eastern, so to a degree this is expected.

Is there any therapies on the horizon that might restore my ability to handle dairy?

Edit: Product like lactaid don't work - make me just as sick.

cucciaman25 karma

Hi /u/KaneHau!

There is a very strong link between microbiome and lactose intolerance. One of the hypotheses is that our ability to digest lactose via the lactase enzyme is not only genetic but also microbiome mediated.

With that being said, one of the avenues that is being explored by researchers is whether it is possible use probiotics to boost lactose digesting bacteria to help with lactose intolerance, and indeed, early research is showing positive results, but more research is needed.

I think this is a good summary for you to check out and I hope it helps.


curlycanadian_12 karma

Do we have any idea what causes IBD? Can someone develop it anytime in their life or is it something that is understood to be something developed when one is young?

cucciaman24 karma

Do we have any idea what causes IBD? Can someone develop it anytime in their life or is it something that is understood to be something developed when one is young?

Hey /u/curlycanadian_,

Hello from Montreal to my fellow Canadian!

In general, there are 3 components to the development an illness like IBD. Genetics, the microbiome and the external environment (lifestyle, stress, diet, etc.). All of these factors play a role, but more research is still needed.

For example, while genetics play an important role in IBD, the individual's environment also has a large impact. What we eat and how we live our lives affects our bodies, our immune system and our microbiome. In addition, most people develop IBD when young and as you age the likelihood of an autoimmune disease like IBD decreases, but it is possible to develop it at any point in your life. Common triggers are stressful lifetime events such as the death of a loved one or a traumatic accident.

For example, children of Asian immigrants are much more likely to develop IBD than their parents, despite having a similar genetic makeup. One of the suspected causes is the shift from an Asian to a Western Diet causes unbeneficial changes to the microbiome, producing a higher likelihood that these individuals will develop IBD.

Another interesting study on this topic is the GEM study. In this study, researchers are following a group of people who are first-degree relatives (Ex: siblings) of those who have developed Crohn's to determine which lifestyle and biological factors lead to the development of Crohn's over time.

While more research as to what is most preventative is still required, diets such as the Mediterranean diet or those high in fermented foods are much less inflammatory than the standard Western Diet. In addition, avoiding ultra processed foods has been shown to reduce the risk of developing IBD.

I hope this gave you some insight on the topic.


MercuryAI11 karma

Do you know which gut bacteria types, or gut bacteria factors (such as ratios of different bacteria, etc) most significantly impact weight gain?

Likewise, do you have a favorite probiotic that you like?

cucciaman14 karma

Hi /u/MercuryAI!

There are a few aspects of the gut microbiome that have been associated with obesity. One of these is an increased ratio between bacteria in the Firmicutes phylum to those in the Bacteroidetes phylum. It is thought that the increased number of Firmicutes lead to greater fermentation of carbohydrates in your diet and provide an extra source of energy. For a more detailed look the known links between obesity and the microbiome, I’d suggest the following paper (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683132/)

mauut10 karma

I took a viome(?) test a few months back - what is your perspective of some of those offerings in the marketplace ?

cucciaman10 karma

Interesting you should ask, we actually run a startup called Phyla, combining microbiome health tests, a digital health app, and personalized recommendations, so admittedly we're a bit biased on the perspective of this market. While I won't comment on Viome specifically, there is merit behind taking a test to assess the diversity, composition, and relative abundance of your gut microbiota. With Phyla's test, we set ourselves apart in a meaningful way by being the only service to offer longitudinal testing, as we take three samples over the course of about two weeks (and for the price comparable to what other companies are offering for one test). The gut microbiome is so dynamic that testing at a single time point is not really indicative of your health state. Our extensive research showed that three is the magic number, so we are confident in the accuracy of our findings as we pair then with self-reported measures such as diet, exercise, sleep, mood, and medication use. Hope that answers your question on our perspective and justifies why we think these solutions (especially ours ;) ) are worth it!

edit: typo

onegirlandhergoat9 karma

Does consuming fermented foods and drinks have a significant impact on the gut microbiome? Is eating too much detrimental?

cucciaman23 karma

Hi /u/​​onegirlandhergoat,
There was an excellent study published recently that looked at how fermented foods, such as yogurt (which contain probiotic bacteria), alter the gut microbiome. In this study, they showed that fermented foods increased the diversity of bacteria found in the gut. Surprisingly, few of the new bacteria in the subjects’ guts were from the fermented foods in their diets. The study suggested it was because of the other components of the fermented foods, such as compounds produced during fermentation, that provide a more hospitable environment to new bacteria.
- https://pubmed.ncbi.nlm.nih.gov/34256014/

4InchesOfury8 karma


grizzzl4 karma

1st: Do these probiotic pills that claim to have x amount of active bacteria cultures really do something or do they just die on the way to the gut?

2nd: If the Answer to the 1st question is yes, then why does one have to keep taking the probiotics? Once all the cultures reached your gut and are established after.. Idk, say 2 weeks of taking it, then they should just be part of your gut microbiome right?

cucciaman6 karma

Hi /u/grizzzl!

Part of your question was answered in one of my previous posts here (https://www.reddit.com/r/IAmA/comments/pt9zsp/comment/hdv0ky1/?utm\_source=share&utm\_medium=web2x&context=3).
Now to answer some of your other questions. First, the probiotic bacteria do make it through your stomach and into your gut. For example, two studies I found (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524715/ and https://pubmed.ncbi.nlm.nih.gov/30193112/) were able to detect small amounts of probiotic bacteria in stool samples from human patients. The increased probiotic bacteria levels were very transient though with, with the level returning to the person’s baseline after cessation of the probiotic. The transient increase in probiotic bacteria is a fairly consistent finding from these types of studies.
From these studies, it looks like the probiotic bacteria were not able to colonize the subjects gut microbiomes. As I mentioned in my previous post, this may have to do with the highly personalized nature of the gut microbiome. Future research is needed to figure out what criteria are required to determine if a person will successfully respond to a specific probiotic.

BridgetteBane3 karma

So if gut health can impact mental health... How exactly do you fix it? My docs never seem to have any idea it's even A Thing that gut health can be related to depression.

cucciaman14 karma

There's currently a lot of research pointing to mindfulness approaches because they help the brain and gut basically realign. Mindfulness-based stress reduction is all about present-moment awareness, like a form of mindful meditation, that can be used for people with gut health issues accompanied by mood disorders like IBS and anxiety. You let your body feel what it needs to feel, and you accept your physical thoughts, feelings, emotions and let them come and go without rumination or judgement. This kind of exercise is considered an intensive training program (~8 weeks), but that main facet of conscious focus on your current experience is central to it and can be done at home with some practice. You can also try journaling, yoga, and meditation to center yourself, even in absence of any gut health issues.
I would definitely start with body scanning videos on youtube; there are some really great 10-minute ones. The most important thing with mindfulness-based exercises is having an open mind about it, because if you're skeptical, your brain basically won't let it work. -LC

she-asks-questions3 karma

what got you interested in microbiomes? also, any advice for wannabe scientists?

cucciaman2 karma

speaking for myself, I've dealt with gut health issues over the years and my aunt is a longtime Crohn's disease warrior. Friends of mine have also suffered with IBS. I have always had a passion for healthcare and helping others, so once I learned about digestive health and the microbiome during my bachelor's, it all clicked. I was really intrigued by the prospect of merging my interests in gut health and my desire to support patients with information, and the more I learned about the amazing world of microorganisms working in the gut, the more I wanted to share my knowledge with others!

Advice: don't be afraid to try something outside your comfort zone or area of expertise- reach out to peers or professors who do something that fascinates you and have a chat! Push yourself to try out different fields of interest and follow this up with regular reading of new literature so you're always in the know about things that you have passion for :) hope that helps! -LC

the_animaI2 karma

Does having an ileostomy affect one’s mental health and/or immune system?

cucciaman5 karma

Does having an ileostomy affect one’s mental health and/or immune system?

It can. Survey studies have shown that ostomates tend to have poorer mental health than the general population. There are so many factors involved in having an ileostomy, like disease state before and after the surgery, coping with the new condition of having a stoma bag, navigating your healthcare journey, etc, that can contribute to changes in quality of life, and different studies report lower or about the same levels of quality of life compared to healthy people.
Also, research on infants who had an ileostomy showed that their gut microbiome shifted in terms of diversity and composition, which could have negative effects on their immune development in theory, but the researchers found that key bacterial species like Faecalibacterium were there enough to help good bacteria propagate and properly develop the immune system after surgery. Research still has to be done in this area but I like the question! -LC

tr0tle2 karma

I've been diagnosed with PSC (primary sclerosing cholangitis) about a year ago. And there is talk and papers in that your gut bacteria could be the source of all problems related to this disease. How is the research on auto immune disease and your gut going? As they seem more tied in then previous expected

cucciaman4 karma

Hi /u/tr0tle!
Several studies have identified links between the gut microbiome and autoimmune diseases. Our current understanding of this is that the gut microbiome has some form of two-way relationship with the immune system, which in turn is the direct driver of autoimmune illness. Therefore, the gut microbiome is indirectly connected to these illnesses via the immune system. While there is a strong connection between the gut microbiome and autoimmune diseases, further research is needed to determine how to alter the bacteria in your gut to alleviate the disease symptoms.

RPM_Rocket2 karma

Can an "apple a day" really keep the doctor away? Seriously, can a a daily apple provide enough insoluble fiber and pectin to help gut health?

cucciaman11 karma

Interesting question! Insoluble or indigestible fiber is awesome for gut health because gut bacteria just love it, using it to create energy and beneficial byproducts such as short chain fatty acids, so it's certainly important to get enough of it from a variety of sources. One apple has approximately 4.4 g of fiber, whereas the recommended daily intake of fiber is about 25 g. So while apples with the skin on are a solid source of both soluble and insoluble fiber. The pectin certainly is valuable! So have an apple a day, but also have some whole grains, beans chia seeds, broccoli, and other whole foods to get enough fiber to promote gut health! -LC