Gut Microbiome Changes in Chronic Pain — Test and Treat?
'There is now a whole list of pain conditions that appear to have these signatures, including postoperative pain, arthritis, neuropathy and migraine to name a few,' Robert Bonakdar, MD, director of pain management, Scripps Center for Integrative Medicine, San Diego, told Medscape Medical News .
Fibromyalgia and complex regional pain syndrome (CRPS) are also on the list.
A team led by Amir Minerbi, MD, PhD, director of the Institute for Pain Medicine, Haifa, Israel, and colleagues published one of the first articles on gut changes in fibromyalgia. They noted that the gut microbiome could be utilized to determine which individuals had the condition and which did not — with about a 90% accuracy.
The team went on to show that transplanting gut microbiota from patients with fibromyalgia into germ-free mice was sufficient to induce pain-like behaviors in the animals — 'effects that were reversed when healthy human microbiota were transplanted instead,' Minerbi told Medscape Medical News .
Further, in a pilot clinical study, the researchers showed that transplanting microbiota from healthy donors led to a reduction in pain and other symptoms in women with treatment-resistant fibromyalgia.
Most recently, they found significant differences in the composition of the gut microbiome in a cohort of patients with CRPS from Israel, compared to matched pain-free control individuals.
Notably, two species — Dialister succinatiphilus and Phascolarctobacterium faecium – were enriched in patients with CRPS, while three species — Ligilactobacillus salivarius, Bifidobacterium dentium, and Bifidobacterium adolescentis – were increased in control samples, according to their report published last month in Anesthesiology .
'Importantly,' these findings were replicated in an independent cohort of patients with CRPS from Canada, 'suggesting that the observed microbiome signature is robust and consistent across different environments,' Minerbi told Medscape Medical News.
Causal Role?
'These findings collectively suggest a causal role for the gut microbiome in at least some chronic pain conditions,' Minerbi said.
However, the co-authors of a linked editorial cautioned that it's 'unclear if D succinatiphilus or P faecium are functionally relevant to CRPS pathophysiology or if the bacteria increased in healthy control samples protect against CRPS development.'
Minerbi and colleagues also observed that fecal concentrations of all measured short chain fatty acids (SCFA) in patients with CRPS were lower on average compared to pain-free control individuals, of which butyric, hexanoic, and valeric acid showed significant depletion.
Additionally, plasma concentrations of acetic acid showed significant depletion in patients with CRPS vs control individuals, while propionate, butyrate, isobutyrate and 2-methyl-butyric acid showed a trend toward lower concentrations.
The quantification of SCFA in patient stool and serum is a 'notable advance' in this study, Zulmary Manjarres, PhD; Ashley Plumb, PhD; and Katelyn Sadler, PhD; with the Center for Advanced Pain Studies at The University of Texas at Dallas, wrote in their editorial.
SCFA are produced by bacteria as a byproduct of dietary fiber fermentation and appropriate levels of these compounds are important to maintain low levels of inflammation in the colon and overall gut health, they explained.
This begs the question of whether administering probiotic bacteria — many of which are believed to exert health benefits through SCFA production — can be used to treat CRPS-associated pain. It's something that needs to be studied, the editorialists wrote.
Yet, in their view, the 'most notable achievement' of Minerbi and colleagues is the development of a machine learning model that accurately, specifically and sensitively categorized individuals as patients with CRPS or control individuals based on their fecal microbiome signature.
The model, trained on exact sequence variant data from the Israeli patients, achieved 89.5% accuracy, 90.0% sensitivity, and 88.9% specificity in distinguishing patients with CRPS from control individuals in the Canadian cohort.
Interestingly, in three patients with CRPS who underwent limb amputation and recovered from their pain, their gut microbiome signature remained unchanged , suggesting that microbiome alterations might precede or persist beyond symptomatic phases.
Test and Treat: Are We There Yet?
The gut microbiome link to chronic pain syndromes is a hot area of research, but for now gut microbial testing followed by treatment aimed at 'fixing' the microbiome remains largely experimental.
At this point, comprehensive gut-microbiome sequencing is not a routine, guideline-supported part of care for fibromyalgia or any chronic pain condition.
'Unfortunately, even for doctors interested in this area, we are not quite at the state of being able to diagnose and treat pain syndrome based on microbiome data,' Bonakdar told Medscape Medical News .
He said there are many reasons for this including that this type of microbiome analysis is not commonly available at a routine lab. If patients do obtain testing, then the results are quite complex and may not translate to a diagnosis or a simple microbiome intervention.
'I think the closest option we have now is considering supplementing with commonly beneficial probiotic in pain conditions,' Bonakdar said.
One example is a preliminary fibromyalgia trial which found that supplementing with Lactobacillus , Bifidobacterium, and Saccharomyces boulardii appeared to have benefit.
'Unfortunately, this is hit or miss as other trials such as one in low back pain did not find benefit,' Bonakdar said.
Addressing gut microbiome changes will become 'more actionable when microbiome analysis is more commonplace as well as is the ability to tailor treatment to the abnormalities seen on testing in a real-world manner,' Bonakdar said.
'Until then, there is no harm in promoting an anti-inflammatory diet for our patients with pain which we know can improve components of the microbiome while also supporting pain management,' he concluded.
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Per a new analysis in JAMA Psychiatry , female physicians — who may face additional stressors, including childcare burdens, sexual harassment, and unequal pay — have a 53% higher suicide risk than female general population. The study also found that physicians who die by suicide exhibit several distinct characteristics compared with nonphysicians who die by suicide. The physicians were more than twice as likely to experience job problems and 40% more likely to have legal issues. Physicians are also particularly at risk of taking their own lives due to their access to lethal means. The JAMA Psychiatry study found that physicians were 85% more likely to die by poisoning and more than four times more likely to use a sharp instrument than the general population. While groups like the American Hospital Association and the American Medical Association (AMA) have specifically addressed the topic for healthcare workers, a 2025 Medscape survey found 6 out of 10 physicians see suicide as a significant issue for the medical profession — while 52% believe the profession doesn't properly confront it. The paths to suicide risk are heterogeneous, but physicians face many of them — mental health conditions, prolonged high-stress environments, access to lethal means, discrimination, and more. 'Under a stressful environment, things are going to crack, and there are cracks everywhere,' one suicidal physician with a specialty in surgery told Medscape Medical News . 'Crumbling on the Inside' Doctors across the healthcare field continue to raise issues around burnout, unrealistic demands, and little space for self. 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Everything was crumbling on the inside, but I looked put together on the outside.' Shabbir feared that admitting her depression, even taking one Lexapro pill 'could potentially be career-ending.' 'Why are we making people in medicine feel like they have to have it all together,' she asked, 'to the point where the only way out that they see can be the end?' Multiple experts Medscape Medical News spoke with for this article emphasized the differences between burnout, an occupational phenomenon of chronic physical and emotional exhaustion, and clinical and diagnosable mental health conditions such as anxiety, depression, and posttraumatic stress disorder. But physicians we spoke to regularly mentioned both in relation to suicidality, suggesting the two are deeply entangled. For example, burnout has been linked to the amount of student loan debt a physician carries. And in the depths of mental illness, catastrophic thinking around financial stress can take root, says psychiatrist Michael Myers, MD, author of Why Physicians Die by Suicide . For physicians, it can about everything — from mistakes or debt to feeling like a failure or feeling like you don't belong. 'At that point, it doesn't take a stretch to think, 'I'd be better off dead.'' Training to Suffer Pamela Wible, MD, an Oregon physician who specializes in physician suicide and experienced suicidal ideation in medical school, says struggles can start early. She describes a 'soul-level mismatch' between medicine's ideals and its harsh 'indoctrination' of hazing, bullying, abuse, and sleep deprivation. She says students become 'automatons' focused on tests and memorization. Pamela Wible, MD Christine Moutier, MD, now chief medical officer at the American Foundation for Suicide Prevention (AFSP), entered medical school as a piano performance major. With little science background, she quickly felt in over her head. Raised to keep personal struggles private, she felt out of place and unprepared compared with classmates from medical families. Christine Moutier, MD 'You have an illusion that everybody else is just so much more together than you are,' Moutier said. As anxiety took root, so did an eating disorder. 'I never learned to sit with discomfort, self-reflect, talk to a peer, or even journal,' she explained. She just pushed herself to work harder. After her second year, Moutier got married and deferred her first clerkship, which made her feel even further behind. On the first day of her third year, she found she couldn't think clearly or function. She went to her dean's office intent on quitting medicine. 'My brain was disorganized. It had been 2 years of spiraling psychiatric illness that could have been life-threatening — both from the eating disorder's physical toll and the high suicide risk tied to untreated anxiety,' she said. Moutier took a year off. 'I couldn't even watch ER. It would trigger a panic attack. Med school felt like torture,' she recalled. As she struggled to find her path, she experienced suicidal ideation. But with therapy, she recovered, eventually returning to medicine before joining AFSP. 'My passion for physician and med student mental health — and suicide prevention — is what kept me in academic medicine,' she said. Clearly, systemic stressors persist beyond medical school. The surgeon who spoke to Medscape Medical News anonymously said that in residency 'the learning curve is so incredibly steep,' there is simply 'too much to learn.' He described witnessing racism, abuse, physicians throwing surgical tools across the operating room, and general rule breaking. These incidents took place at top medical centers where, he said, he faced retaliation and unfair evaluations when he spoke out. He experienced depression and suicidal thoughts, ultimately resigning from his program. 'I felt powerless, like I no longer had a place in this world,' he said. A Path Toward Openness and Education Today, research and supportive approaches to the issue of physician suicide have grown substantially. But this wasn't always the case. In 1962, when Myers was in medical school, he lost a roommate to suicide. He remembers announcing the terrible news to his class. His professor responded, ''Let's get back to the Krebs cycle.' It was a message that we don't talk about this.' Now, Myers says he regularly invites young physicians who have experienced mental health struggles, suicidal thoughts, or have recovered from substance use disorders to speak during medical school or residency orientations. Christine Sinsky, MD, former vice president of professional satisfaction at the AMA, says this type of self-disclosure is 'one of the most powerful things I'm aware of,' as it encourages others to speak up. 'It's important to tell medical students they are entering a high-reward yet high-risk profession.' Christine Sinsky, MD But this level of honesty isn't always easy to come by. Myers says deans of medical schools still push back about this type of discourse, sometimes fearing that open conversation will scare medical students or trainees. Myers insists it does the opposite. Removing Barriers to Care Despite this type of progress, there are still barriers that keep physicians quiet about their struggles. Historically, mental health questions on medical licensing and hospital credentialing applications have precluded physicians from seeking support around mental health or suicidal ideation out of fear of potential penalization. In 2020, the Dr. Lorna Breen Heroes' Foundation was founded by the family of Lorna Breen, MD, an emergency room physician who died by suicide. The group's mission is to eliminate barriers to mental health care and reduce stigma, empowering physicians to seek the care they need. The group has particularly worked to eliminate stigmatizing language around mental health from 34 state licensing organizations' licensing boards and over 50 hospitals' credentialing applications. Today, more healthcare facilities offer dedicated mental health services exclusively for physicians and trainees that aim to reduce other barriers like confidentiality concerns, time constraints, and ease of access. Some operate independently from medical schools or use separate electronic medical record systems to enhance privacy. 'I've never heard of a doctor with a cancerous tumor who didn't go to see an oncologist, but there are still doctors who take their lives without ever having had an assessment,' said Myers. Yet access to mental health care remains challenging, says Moutier. Stigma and fear are still pervasive. Some physicians report seeking help but downplaying symptoms, including suicidal thoughts. More Work to Be Done Myers commends major medical organizations for their work in suicide prevention and says that a culture shift requires 'enforced changes.' One of these, which has been widely recommended, is placing limits on working hours. Sleep deprivation not only compromises patient care but also significantly increases the risk for mental health conditions. One study published in PLOS One found that decreases in sleep among residents and medical trainees were linked with an increased risk for suicidal ideation. Institutions are required to adhere to the 80-hour workweek limit for residents set in 2003 by the Accreditation Council for Graduate Medical Education (ACGME). In 2017, the group introduced Common Program Requirements focused on resident well-being. In reality, there is evidence that some residents feel pressure to exceed these guidelines without reporting it. Some told Medscape Medical News that work-hour limits and programs to improve physician well-being, while promising, are not always followed. In an emailed statement, the ACGME told Medscape Medical News , 'Requirement compliance is primarily reviewed through routine site visits, faculty and resident surveys and reporting by the program directors and designated institutional official. Complaints can be filed by anyone and can be done so anonymously through the ACGME Office of the Ombudsperson.' Still, Wible says the system profits from residents' overwork and exploits their people-pleasing tendencies. Shabbir also stresses that physician suicide is a community problem. 'As patients and providers, we think that we're on different sides of the exam table, but we're on the same side. We're all hurting together.' Shabbir founded the Early Career Physicians Institute in 2023 to coach physicians through burnout and perfectionism. Wible, who runs a suicide support line and groups for physicians, believes strongly in the power of peer support. One physician who experienced suicidality told Medscape Medical News that 'everything rapidly changed for the better' once he joined a peer support group. 'It felt like a rocket launch. We rose out of the muck together.' Myers says the openness about mental health among the next generation of healers keeps him optimistic. 'I've had many doctors tell me, 'I read someone's story and realized I'm not alone,'' he said. 'They feel less ashamed of seeking help themselves. That's incredibly powerful.' If you or someone you know is in crisis, help is available. Utilize the below services.
