Gut Microbes Could Soon Diagnose and Explain The Cause of IBS and IBD

By Anna Groves | December 20, 2018 4:18 pm
IBD and IBS

(Credit: sedat seven/shutterstock)

Doctors have long scratched their heads over the causes and cures for two common diseases of the digestive system: IBS and IBD. But research out today in Science Translational Medicine takes a leap forward in explaining these conditions, thanks to a major undertaking to sequence the gut microbiomes of almost 2,000 people.

Difference Between IBS and IBD

Irritable Bowel Syndrome, or IBS, is thought to affect as much as 20 percent of the world’s population, while its cousin, Inflammatory Bowel Disease or IBD, is less common (fewer than 1 percent of the population) but more severe. The two have similar symptoms, but because one is characterized by its namesake inflammation (IBD) and the other isn’t (IBS), their treatments are very different.

When a patient reports abdominal pain, constipation or diarrhea, doctors conduct invasive tests like blood samples and colonoscopies to look for signs of inflammation. If they find it, the patient has IBD, and treatments are aimed at reducing that inflammation. Crohn’s disease and ulcerative colitis are both types of IBD.

But if doctors find nothing? That’s IBS. IBS is a bit of a catch-all diagnosis for when there’s no inflammation — and really no other abnormalities that might explain a patient’s symptoms. Current IBS treatments revolve around alleviating symptoms and hoping for the best.

Although scientists recently identified a possible genetic trigger of IBD in mice, the root causes of both diseases are currently unknown.

Poop Microbes Reflect Colon Microbes

Mounting evidence shows that microbes play a role in gut health, and previous research has showed that IBS and IBD patients have different microbiota than healthy people. That’s why a research team in the Netherlands wondered how the two would compare to each other, and if they could be used for diagnosis.

“We thought, let’s see if the microbiome, or gut composition, can become a biomarker so we can design new tests in order to distinguish these two diagnoses,” says Arnau Vich Vila, computational biologist at the University Medical Center Groningen in the Netherlands.

“We would reduce the number of colonoscopies; saving time, saving money and also improving the diagnosis so that the patient doesn’t have to go through this kind of procedure,” says Vich Vila.

The team set about sequencing the microbiomes from almost 1,800 people: 350 with IBD, 410 with IBS, and 1,000 healthy people as a comparison. But to do this, they needed to collect 1,800 microbiomes. That’s a lot of poop.

They found their participants through three different established banks of volunteers with well-established medical information for use in population studies. If you’ve ever peed in a cup at the doctor’s office, you can use your imagination to figure out how fecal samples are collected. But as an added challenge, fecal samples can’t be kept at room temperature, because that would allow certain bacteria to grow, interfering with the study results.

“So we asked all of them to collect the sample at home, put it in the freezer, and then we were driving around the Netherlands to pick up these samples,” says Vich Vila.

They used a genetic tool called shotgun metagenomic sequencing to sequence the DNA of the bacteria living in each sample, a common technique used to identify bacteria species in big samples. But they didn’t just identify the species – they looked at how abundant each was, how fast each grew, and what functions each performs in the gut.

upset stomach IBD and IBS symptoms

(Credit: Emily Frost/shutterstock)

IBD Bacteria, Different from IBS Bacteria

They found that people with IBD and IBS had substantial overlap in which microbes they had in their guts, and both were different than their healthy peers. And Vich Vila says the group was surprised to find such an overlap in the IBS and IBD microbes, because of how fundamentally different the two diseases are.

But the researchers also found consistent microbial differences between IBS and IBD patients, suggesting microbiome analysis could soon be used to diagnose IBS and IBD – and could start to explain the differences in the conditions.

For instance, both IBS and IBD patients had reduced numbers of some known beneficial gut bacteria, while only patients with Crohn’s disease had increases in bacteria like Escherichia, known to invade the gut’s mucus lining and cause problems (you know this one from the “E” in E. coli.) Likewise, there were certain bacteria that only the IBS patients had in increased amounts.

The microbiomes were different in other ways, too. The genetic diversity within individual bacteria species was sometimes different, as were the growth rates. Patients with IBS and IBD also had much more virulent bacteria than people with healthy guts – bacteria that do things like evade or suppress their host’s immune system. And patients with Crohn’s, specifically, had more bacteria that had antibiotic resistance genes than any of the other groups.

They also compared the diagnostic abilities of their new microbiome data to that of a currently used diagnostic test for IBD: whether a patient’s stool contains a biomarker of inflammation called calprotectin. Their microbiome test did better at predicting whether a patient had IBS or IBD than did the old test.

What Bacteria Do In Your Gut

What a bacterium does is programmed in its DNA just like any other living organism. So the researchers also wanted to know if their huge genomic dataset could tell us not just which bacteria are in which person’s gut, but what they are up to – especially if what they’re up to is making people sick. Figuring this out would really blow open the possibilities for understanding these two rather mysterious conditions.

They found many functional changes between the IBS, IBD, and healthy patients. For instance, in patients with Crohn’s disease, there were more bacteria breaking down sugars and fewer kickstarting fermentation. That causes the inflammation. Meanwhile, in patients with IBS, there were more bacteria than normal focused on fermentation and breaking down carbs.

This latter point caught the attention of William Chey, University of Michigan professor and practicing IBS specialist, who was not involved in this study. “It’s something I’ve been wondering about for quite a while,” says Chey, explaining that IBS patients often complain of bloating, and bloating is often caused by fermentation. “A question’s always been, could the microbiome provide an explanation for that?”

“So what they found – alterations in the microbiome which would explain increased levels of fermentation or altered fermentation in IBS patients – is really interesting,” says Chey.

Gut Solutions For The Future?

Valerie Collij, co-lead on the study, researches and practices medicine at University Medical Center Groningen. “As a clinician, I would say that this is the base for future treatments,” she says. “We can use this information to get dietary interventions, or pro- and prebiotics, or even fecal transplants that are based on the gut microbiome composition. That would be great. But we are nowhere near there, yet, I would say.”

“But what we are really close to now is using microbiota as a diagnostic tool,” adds Vich Vila.

Chey is excited about where these findings could lead IBS and IBD research in the future. “It’s really been the Holy Grail, looking for the characteristics of the microbiomes that might be linked to the pathology that we see in the clinic,” he says.

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  • OWilson

    Surprisingly, there is no mention of diet and personal habits, alcohol, sleep patterns, drugs, stress levels, exercise or lifestyle in the article.

    Sometimes a these acronym “diseases” are merely “conditions”, that can be resolved with a balanced diet, exercise, adequate rest, and a reduction in stress?

    • JES

      Sometimes maybe, but other times not. It’s a bit dangerous to claim a condition can be solved by lifestyle changes when there is no evidence (yet) for that.

      • OWilson

        Speaking from personal experience only.

        When I was a young man running a business, raising a family and on the road for extended periods of time with no vacations, I had a lot of conditions, IBS, OA, Elevated PSA, GERD and so on.

        Not until I changed my diet, personal habits (cut down on coffee) lost some weight, and got regular exercise, did these conditions disappear, one by one.

        Except for a couple of broken bones, I haven’t seen a doctor, or needed pills in over 30 years.

        Never felt better!

      • Mike Richardson

        Exactly. Be wary of taking advice from someone who reports avoiding regular medical care for decades. Many people who go that route don’t find out they have heart disease until they experience their first (and often also last) heart attack. Healthy eating, excercise, and a positive outlook are all important factors in a healthy lifestyle, but regularly checking with professional health care providers is vital to detecting and treating chronic conditions before they become serious, or even life threatening.

        • OWilson

          I don’t pretend to be a doctor, so my original comment was posted in the form of a question, not as “advice” :)

          But I and my young family were treated by a popular pill dispenser physician to the point that we were all on something, valium, teenage acne cures, supplements for imagined allergies and so on.

          My dear wife was treated by drugs and a hysterectomy, for a condition (cancer we found out later) and once we got her away from our doctor and his pal, the specialist, she was immediately put into hospital where she belonged and died a few weeks later at a distressingly early age.

          At great personal cost, we learned that dependence on daily, routine prescribed drugs, except for lifesaving conditions, was not healthy in the long run and we all eschewed them, and are now all living healthy drug free lives.

          See:

          “How Good Intentions Contributed to Bad Outcomes” – The Opioid Crisis –
          mayoclinicproceedings, 2018

          Abstract. The opioid crisis that exists today developed over the past 30 years. The reasons for this are many. Good intentions to improve pain and suffering led to …

          • Mike Richardson

            I am genuinely sorry to hear you lost your wife in such a tragic manner. As much as I love my own wife, I can’t imagine how awful that would. Despite our many differences, you do have my sympathy for that.

            My own family has genetic predispositions for diabetes, hypertension, and heart disease, and while diet and exercise can definitely help with this, prescribed medication and regular checkups are literally lifesavers for these conditions. Any one of those conditions can silently kill if undetected, but properly treated, they can be reduced or even reversed. Maybe you have good genes, but despite your bad experiences with the medical profession, you might want to at least be checked to avoid finding out too late that you have a potentially life threatening condition. Your point about opioids and other overly prescribed medications is certainly valid, however.

            I personally believe access to affordable quality healthcare, including diagnostic and preventative care, should be a basic human. But if you choose to decline it, that too is your prerogative.

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          • OWilson

            As a lifetime keen student of science I am aware of the risks associated with common maladies, and I don’t take them lightly.

            However my own personal views are informed by experience.

            In another personal example of socialized medicine at work, as a young man I fell awkwardly while playing hockey. I was virtually prone and in severe pain. I was told I had DA (Degenerative Arthritis) which only surgery to fuse the spine could alleviate and in the meantime was prescribed heavy drugs for the pain.

            I read everything I could on the subject of back pain and came upon “Dr Hamilton’s Back Book” which changed my life.

            He, a doctor, said that the human body, would heal most common back pain (and most other common maladies) if the body is left to repair itself, without immune response depressing drugs, and gradual exercise. He said whatever “treatments” you are taking at the time of this natural healing, hot or cold compresses, chiropody, drugs, activity or bed rest, and when the pain finally goes away, that treatment will be forever imprinted on the average person as the most effective cure. (If you talk to former back pain sufferers they all have their favorite, often contradictory “cures”.)

            Truth is, and good physicians know this, people expect and demand treatment, and telling them to go home, gently exercise, and wait the six weeks or so, is a none starter. :)

            I have a close family member, with the same genetic make up, but he is captive to clinics and drugs for those “dispositions” you mention above which we all have as we age.

            No doubt I would be given a list of these “dispositions” if, as a healthy, active person living well past my actuarial “best before” date, if I asked a doctor to examine me. (I could probably give him the list in advance :) But dispositions are not diseases, and it is too late for me to die before my time from such :)

            As to your basic human right requirement of health care, you might add, food, clothing, shelter, education and many other life essentials, like transportation to colleges, hospitals, and day care for your kids, while you are there.

            But you’ll have to figure out who the poor suckers are who are going to have to work to provide it to everybody.

            And no, build up spiraling National Debts to dump on future generations, is not a good long term solution!

            There’s still no “free lunch”. :)

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    • Jo

      Lifestyle changes can be a successful part of managing such conditions, but, like many other situations, what suits one is not appropriate for another. As somebody with IBS (thankfully not IBD), changes in diet certainly helped, but there is a lot of trial and error involved in the long term management.

      I’m excited to see where this work goes next.

    • Karl Bode

      Not entirely accurate. Often these folks can almost live a normal life if they adhere to very strict diets, but that doesn’t mean they’re otherwise healthy, or that these conditions are exclusively caused by bad habits.

      Though your point about diet being hugely important is spot on.

      • OWilson

        Of course not, some drugs are essential to life, but you don’t have to be a genius to understand that the two biggest commercial growth industries, the refined, processed food conglomerates and the pharma industry which redresses the consequences of eating same, have produced a nation which has an obesity crisis and a drug dependency crisis. :)

        • Karl Bode

          Oh yeah, no disagreement there.

          Was just pointing out that IBS and IBD both have underlying causes that go beyond our generally terrible diets and may not be resolved by better habits alone.

          We just don’t know what the causes of these disorders really are yet because we don’t fully understand the microbiome and the gut yet, so we give them catch all names that don’t mean much.

          But yeah, these folks certainly don’t get any help from a country with systemically bad diets and even worse medical care.

      • gimpi1

        IBD seemed to run in my family. Then, my aunt, after suffering for years, was discovered to have Ceilac. After her diagnosis, several other folks got tested, and discovered they either had full-blown Ceilac or were gluten intolerant. Diet change not only cleared up the digestive problems, but eliminated rashes, chronic pain and fatigue.

        Now, I know this is specific to my family, but since diagnosing Ceilac just requires a blood test these days, if someone is having chronic digestive problems, consider getting tested.

  • liebran

    I have IBS (years) finally after reading a research article on low thyroid pts. with IBS, they recommended a certain probiotic. I tried this, and after 2 weeks-the difference is remarkable. No bloating, etc. I had to search through a lot of probiotics until I found one that had the one-bacillus clausii.

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