For decades, physicians have puzzled over the contradictory effects of smoking on inflammatory bowel diseases (IBD). Smoking makes Crohn’s disease worse, but appears to protect against ulcerative colitis (UC). Recent research from RIKEN has uncovered a surprising mechanism: smoking alters the gut environment in a way that allows oral bacteria such as Streptococcus mitis to colonize the colon, where they shape the immune response (Miyauchi et al., 2025).1 These findings may help guide the development of safer therapies for colitis and may also shed light on the inflammation associated with microscopic colitis (MC). The study found that: 1. Smoking reshapes the gut microbiome via metabolites. Smoking produces metabolites such as hydroquinone, which allow oral bacteria, particularly Streptococcus mitis, to take hold in the colonic mucosa. This effect was seen in smokers with UC, but not in ex-smokers, suggesting the change depends on ongoing exposure to smoking compounds. 2. Oral bacteria influence immune responses. When S. mitis was introduced into mouse models:
3. Immune modulation is key. In UC, inflammation is largely driven by Th2 immune responses, so activating Th1 cells creates a balancing effect that reduces inflammation. In Crohn’s, which already involves Th1-driven inflammation, the effect piles on more damage. Similar to MC, Crohn’s disease (CD) can affect any part of the gastrointestinal tract, but in practice it shows a fairly typical pattern of distribution. Large cohort studies (including European and North American IBD registries) give us good estimates of how often each region is involved. Statistics show that for Crohn's disease (at diagnosis):
UC is very different, because it:
For UC, statistics show that:
How does MC compare with these? Similar to Crohn's disease, MC can affect (cause the inflammation of) any organ in the gastrointestinal tract. Although you won't find many references to small intestinal involvement for MC in recent research, many credible, older pathology-focused studies reported frequent small intestinal involvement, especially involving the terminally ileum. Most modern reviews incorrectly refer to MC as a disease of the colon. Why is small bowel involvement ignored in most current literature discussing MC? With such biased treatment, it's no wonder gastroenterologists are confused about MC and its treatment. In 2003, for example, Nature published a research study in its Modern Pathology series, showing that 78% of lymphocytic colitis patients and 50% of collagenous colitis cases (versus 9% of controls) had intraepithelial lymphocytosis (lymphocytic infiltration) of their terminal ileum (Padmanabhan, Callas, Li, and Trainer, 2003).2 That article also mentions duodenal and jejunal changes in subsets of MC patients, and summarizes prior literature describing abnormal duodenal and jejunal findings, including villous atrophy and collagen deposition in some MC patients, again pointing to small bowel immune activation in a fraction of MC cases. How might this research relate to MC?
Experiences shared by MC patients on our discussion and support forum suggests that bacteria commonly found in the mouth, and sometimes trapped by dental procedures (such as root canals) can contribute to MC flares if they reach the gut. The studies suggest that immune balance between Th1 and Th2 cells is critical. MC has been linked to abnormal T-cell activity, so understanding whether S. mitis–like bacteria can shift this balance is highly relevant. The bottom line: The discovery that smoking promotes oral bacteria growth in the gut, altering immune pathways in opposite ways for Crohn’s disease and ulcerative colitis, solves a decades-old puzzle in gastroenterology. For MC patients, these findings highlight the importance of the microbiome-immune connection, and point toward new therapies that could harness microbial modulation—without the dangers of smoking. However, in the absence of dedicated research data, definite conclusions regarding MC, cannot be drawn. We know that when medical discoveries revealed the extent of the risks associated with smoking, many people who stopped a long-term smoking habit developed MC (almost surely due to the stress that resulted). But the unanswered question remains — “Does MC more closely resemble Chron's, or UC?” The evidence suggests that it more closely resembles Crohn's, than UC, but without compelling evidence, we can't be sure. And as we all know as MC patients, what works for some, does not work for all. So there is a possibility that this line of research may well lead to treatments that benefit some of us, but worsen symptoms for others. References: 1. Miyauchi, E., Taida, T., Uchiyama, K., Nakanishi, Y., Kato, T., Koido, S., . . . Ohno, H. (2025). Smoking affects gut immune system of patients with inflammatory bowel diseases by modulating metabolomic profiles and mucosal microbiota. Gut, Published Online First Retrieved from https://gut.bmj.com/content/early/2025/08/06/gutjnl-2025-33492 2. Padmanabhan, V., Callas, P. W., Li, S.. C., and Trainer, T, D. (2003). Histopathological Features of the Terminal Ileum in Lymphocytic and Collagenous Colitis: A Study of 32 Cases and Review of Literature. Nature Modern Pathology, 16. pp 115–119. Retrieved from https://www.nature.com/articles/3880725
0 Comments
Official statistics show women being diagnosed with depression at twice the rate of men, creating the impression that depression primarily affects women. However, strong evidence suggests this diagnostic pattern may contribute to a distortion of reality — men may actually experience depression at equal or higher rates than women, with their suffering remaining largely invisible until it culminates in the most tragic outcome — suicide. Suicide statistics tell a different story. The most powerful evidence that men's depression is severely underrecognized comes from suicide mortality data. Despite receiving depression diagnoses at half the rate of women, men die by suicide at three to four times the rate across virtually all age groups, cultures, and countries. This stark disparity suggests that the 2:1 female-to-male depression diagnosis ratio severely underrepresents the true magnitude of depression in men. The extent of this difference can't be explained by method lethality alone. While men do choose more immediately fatal suicide methods, the sheer scale of the gender gap (consistently 3-4 times higher across populations) points to a massive amount of unrecognized depression in men. These statistics suggest that for every woman diagnosed with depression, there may be one or more men experiencing equally severe depression that goes unidentified by current diagnostic approaches. And there's a good possibility that this pattern may indicate that rather than men experiencing depression at "similar rates" to women, they may actually suffer from depression at substantially higher rates. The suicide data serves as a tragic but revealing endpoint that exposes the disconnect between current mental health services and depression in men. The healthcare system's depression diagnostic criteria are biased against men. Current depression screening tools were developed and validated primarily using female symptom presentations, creating systematic bias against recognizing male depression. Standard instruments like the PHQ-9, Beck Depression Inventory, and Hamilton Depression Rating Scale emphasize symptoms such as sadness, tearfulness, guilt, worthlessness, and withdrawal — characteristics that align closely with how women typically express emotional distress. Male-typical depression symptoms are poorly represented in these diagnostic criteria. When men experience depression through irritability, anger, aggression, risk-taking behaviors, substance abuse, or workaholism, these presentations score poorly on traditional screening methods. This diagnostic bias means that men with severe, potentially life-threatening depression may appear "normal" on standard assessments, while women with similar severity levels receive appropriate diagnoses. The consequences of this diagnostic failure extend beyond individual cases to create systematic underrepresentation of male depression in research, treatment development, and healthcare resource allocation. When depression research and treatment protocols are based primarily on female populations, they are almost surely inadequately designed for males who are experiencing the condition. Our culture hides signs of male distress. Gender socialization creates powerful barriers that not only prevent men from seeking help but also make their depression invisible to others. From early childhood, boys learn that expressing vulnerability, sadness, or emotional need contradicts masculine identity. This cultural programming becomes so deeply internalized that many men genuinely cannot recognize their own depression or frame their distress in psychological terms. When depressed men do visit healthcare providers, they typically focus on physical symptoms such as fatigue, pain, sleep problems, and digestive issues, while avoiding discussion of emotional concerns. Expressing psychological or emotional issues as physical symptoms is known as somatization. And somatization can effectively mask severe depression, particularly when providers lack training in recognizing this behavior as potential mood disorder symptoms. The cultural expectation that men should be stoic and self-reliant means that male depression often remains hidden from family members, friends, and colleagues until it reaches crisis levels. Unlike women, who are more likely to discuss emotional struggles with social networks, men typically suffer in isolation, missing opportunities for early identification and intervention. The bottom line:
Scientists from the University of Tartu in Estonia studied over 2,500 Estonian Biobank samples and found that drugs we took years (sometimes many years) ago can still be detected in our gut microbiome today (Aasmets, Taba, Krigul, Andreson, and Org, 2025).1 And it’s not just antibiotics. Antidepressants, beta-blockers, proton-pump inhibitors (PPIs), and benzodiazepines leave distinct microbial fingerprints, some comparable to the impact of broad-spectrum antibiotics. That means a person’s medication history is a hidden confounder that microbiome researchers (and clinicians) have been overlooking in their work. Does that list of medications look familiar? It should, because it includes many of the medications that some of us have blamed for the development of our microscopic colitis (MC). This study considered long-term medication effects. The research team used shotgun sequencing to analyze 2,509 stool samples from the Estonian Biobank Microbiome cohort, linking each sample to years of electronic prescription records. A smaller cohort (328) from the same original 2,509 samples were used as second samples to see what happens when people start or stop specific drugs. Shotgun sequencing involves DNA sequencing by breaking a large DNA molecule into millions of smaller, random fragments, sequencing the fragments independently, and then using computer algorithms to reassemble these fragments into their original order by identifying overlapping sections. By utilizing this process, scientists can determine the complete sequence of long DNA strings, such as an entire genome. Up until now, at least, most human microbiome studies only control for current medications. This study explicitly modeled past use, allowing the team to test for carryover (lingering) and additive (cumulative) drug effects on the microbiome. The study found that: 1. Medication echoes are common and long-lived. Prior use of several drug classes, including antibiotThe study found that:ics, psycholeptics (notably benzodiazepines), antidepressants, PPIs, and beta-blockers, was associated with persistent shifts in microbiome composition years after the last prescription. In media summaries of the work, the authors note that nearly half of the assessed drugs still showed microbiome associations more than a year after use. 2. Benzodiazepines stood out. Surprisingly, benzodiazepines produced alterations on par with broad-spectrum antibiotics, and different drugs within the same class (for example, diazepam compared with alprazolam) showed unequal microbiome disruption. That heterogeneity matters: “which benzo” or “which SSRI” could leave different long-term microbial signatures (Estonian Research Councilm 2025, October 9).2 3. There are additive effects. The more often (or longer) a medication was used in the past, the stronger its detectable microbiome impact — evidence for dose–history relationships, not mere coincidence. 4. Direction of effect (causality) gets support from follow-up samples. In the smaller subset, starting or discontinuing certain meds led to predictable shifts in specific microbes (for example, with PPIs, SSRIs, and several antibiotic classes), strengthening a cause-and-effect interpretation. (It’s not a randomized trial, but the within-person changes are compelling.) How can non-antibiotics drugs do this? This study result joins a growing body of literature showing that many human-targeted (non-antibiotic) drugs have direct antimicrobial activity or change the gut environment (for example, gastric pH, motility, bile acids) in ways that reshape the microbiome. In vitro screens have found that 24% of tested non-antibiotic drugs inhibit gut bacterial strains, and newer studies show such drugs can weaken colonization resistance against pathogens (Maier, et al., 2018).i The Estonian data extend those insights to real-world, long-term human outcomes The bottom line. The Estonian Biobank study makes a clear case: our microbiomes carry long-lasting imprints of medications — antibiotics and many others. For researchers, past prescriptions are a hidden confounder that must be accounted for. For clinicians and patients, the work encourages thoughtful use and periodic re-evaluation of long-term medications, recognizing that the gut ecosystem may remember them long after we do. References 1. Aasmets, O., Taba, N., Krigul, K. L., Andreson, R., and Org, E. 0. (2025). A hidden confounder for microbiome studies: medications used years before sample collection. mSystems 0:e00541-25. Retrieved from https://journals.asm.org/doi/10.1128/msystems.00541-25 2. Estonian Research Council. (2025, October 9). "Common medications may secretly rewire your gut for years." ScienceDaily, <www.sciencedaily.com/releases/2025/10/251008030953.htm>. Retrieved from https://www.sciencedaily.com/releases/2025/10/251008030953.htm 3. Maier, L., Pruteanu, M., Kuhn, M., Zeller, G., Telzerow, A., Anderson, E. E., . . Typas, A. (2018). Extensive impact of non-antibiotic drugs on human gut bacteria. Nature, 555(7698). pp 623–628. Retrieved from https://pubmed.ncbi.nlm.nih.gov/29555994/
Alpha-gal syndrome (AGS) — the tick-borne allergy to mammalian meat and other animal products, is no longer a regional curiosity. Experts report that cases are moving beyond the Mid-Atlantic and South into the Great Lakes and central U.S., with growing recognition worldwide. The message from front-line researchers and the CDC is clear — even if AGS hasn't been discovered in your neighborhood yet, the odds that it soon may be are rising (McKnight, 2025, October 01).1 Severity of symptoms can vary among patients. Galactose-α-1,3-galactose (alpha-gal), is a carbohydrate present in most mammals (although not in primates). In the U.S., tick saliva, most often from the lone star tick (Amblyomma americanum), carries proteins that deliver alpha-gal and trigger IgE-mediated sensitization. Not all bites trigger the development of AGS, and the severity varies. Susceptibility factors remain unclear. AGS is unusual among food allergies for at least 2 reasons.
Symptoms include:
The CDC now warns AGS can be fatal, and has issued its first clinical guidance. Epinephrine should be readily available and used promptly for systemic reactions. AGS is increasing rapidly. From the first 24-case description in 2009 to an estimated 450,000 reported cases in the U.S. by mid 2023, recognition of this problem has grown dramatically. Awareness may explain part of the increase, but experts also point to more tick bites, primarily due to expanding deer populations (the main host for lone star ticks), land-use changes that increases human–deer/tick contact, and climate-driven deer tick range expansion. Although the lone star tick dominates exposure risk in the U.S., other ticks have been implicated globally (for example, Ixodes ricinus in Europe). Early U.S. data suggest additional species, including the deer tick (Ixodes scapularis) and the Asian longhorned tick (Haemaphysalis longicornis)may also carry alpha-gal or convey similar risk. Allergy symptoms sometimes fade in the long-term. In many cases, sensitization fades over 3–5 years, but each new tick bite can “reset the clock.” Ongoing tick exposure therefore prolongs disease and complicates individual cases. AGS is not covered by the allergy related labeling laws. Avoiding allergenic foods is harder than it sounds, because alpha-gal–containing ingredients are not labeled to identify risky ingredients. Gelatin may be listed simply as “gelatin” without identifying the animal source. Policy proposals to require alpha-gal labeling have been considered, but none have passed. So for now, at least, hidden exposures remain common. In some cases, AGS can pose a special risk for MC patients. Note how closely some of the symptoms of AGS resemble the symptoms of MC, so that AGS reactions might be mistaken for an MC flare, in some cases. Specifically: diarrhea hives (for those of us who have histamine issues associated with MC) Be especially mindful of respiratory symptoms (if they are present), since those are usually not associated with MC, and in some cases they can lead to a fatal outcome. If you suspect that you might have AGS:
And for those of us who don't have AGS: It definitely behooves us to take personal protective measures when in tick habitat, especially around bushes, trees, and tall grass. And remember, ticks can jump. Inspect for and remove any ticks promptly. Taking measures to avoid becoming infected with AGS may seem to be bothersome, but minimizing the risk is much less bothersome than avoiding mammalian meat after an allergy develops. The Bottom line: AGS has moved from a rare curiosity to a mainstream clinical reality. It's tick-initiated, IgE-mediated, delayed in onset, and potentially fatal, but often remits without new bites. As cases spread north and west in the U.S. and continue to surface globally, when outdoors, everyone should remain vigilant, and do their best to avoid tick bites. If infected, patients should recognize that safety gaps in labeling exist, and be especially careful when buying processed foods. Reference 1. McKnight, W. (2025, October 01). Alpha-Gal Syndrome, the Meat Allergy, Expands Its Reach. Medscape, Retrieved from https://www.medscape.com/viewarticle/alpha-gal-syndrome-meat-allergy-expands-its-reach-2025a1000qcz
Official medical guidelines often contain worrisome problems. One of those, for example, is the disparity between minimal vitamin D threshold levels set by official guidelines, and the levels that epidemiological data suggest are optimal for much broader disease prevention. This disconnect is real and has been the subject of growing debate among researchers, clinicians, and patient advocates. Does this risky gap exists because of unintended oversight, or a more systemic incentive problem. Official medical vitamin D guidelines reflect minimal standards. At the core of the problem is the fact that the medical guidelines list minimal thresholds that are designed to prevent acute deficiency disease — not to optimize health. For example, medical guidelines from the Institute of Medicine or Endocrine Society define deficiency in terms of preventing:
These guidelines typically set the sufficiency cutoff around 20–30 ng/mL (50–75 nmol/L). But these levels are based on outdated endpoints and ignore the non-skeletal roles of vitamin D, such as:
By contrast, epidemiological studies routinely associate 40–60 ng/mL (100–150 nmol/L) with lower risks of:
Fear of toxicity has led to overly conservative guidelines. Regulators remain cautious because:
However, numerous studies show that levels up to 100 ng/mL are safe and that daily supplementation of 2000–5000 IU is rarely associated with harm, especially when magnesium and vitamin K2 intake are adequate. Yet, the official upper intake limit remains at 4000 IU/day, a conservative figure not supported by more recent safety data. Guideline selecting committees reflect medical conservatism and risk aversion. Organizations such as the Endocrine Society tend to prioritize:
This conservative approach leads to an unrealistic "wait for perfect proof" mentality, despite real-world, population-level correlations suggesting otherwise. Pharmaceutical and insurance incentives tend to disincentive prevention. While it may be unfair to claim the system is intentionally keeping people deficient to drive healthcare profits, structural incentives do create passive disincentives for prevention:
In this sense, the system, as designed, doesn’t reward optimal public health outcomes—it rewards sick care. Guidelines recommend inadequate testing and diagnostic practices. Routine vitamin D testing is discouraged for the general population under current guidelines, despite:
Note that this is similar to the neglect seen with magnesium testing, where reliance on inaccurate serum levels prevents effective diagnosis and intervention. The message sent to the public is confusing and contradictory. Medical authorities often:
This has led to public confusion, under-supplementation, and persistent population-level deficiency—despite decades of emerging research. So do the guidelines encourage sickness rather than disease prevention? There's no clear evidence of any coordinated conspiracy, of course, but:
all contribute to the persistence of low thresholds that serve institutional interests more than patient well-being. In that light, it's fair to argue the system is not designed to promote optimal health. It manages disease reactively rather than preventing it proactively. Vitamin D levels are especially important for IBD patients. Research shows that vitamin D deficiency affects up to 100% of Crohn's disease patients and 45% of those with ulcerative colitis (Johnson, 2025, May 20).1 The deficiency is not merely a result of disease activity — it likely contributes to its onset. Mechanistically, low vitamin D leads to:
Low vitamin D correlates with increased disease activity, more frequent surgeries, higher relapse rates, and poor treatment responses. A 2023 Cochrane review even found reduced relapse rates in patients supplementing with vitamin D, although evidence quality limited definitive conclusions. Another study followed 5,474 IBD patients for 13 years and found that those with adequate vitamin D levels had significantly reduced bowel resection risks — by 34% in IBD overall and 46% in ulcerative colitis (Dan et al., 2024).2 The takeaway: Despite self-serving and often confusing official vitamin D guidelines:
Additional evidence of the safety of higher doses: The Calgary vitamin D study: was a three year, double-blind, random controlled study (RCT) involving adults aged 55–70, and compared daily doses of either 4000 IU or 10,000 IU of vitamin D (Burt et al., 2019).3 The findings showed that both 4000 and 10,000 IU per day were well-tolerated. Bone density was generally unaffected, but was slightly decreased at the highest does, suggest the safety, but no skeletal benefit at high levels in already sufficient adults. The VIDAMS study (multiple sclerosis): compared 5000 IU per day versus 600 IU per day in relapsing remitting multiple sclerosis patients (Cassard et al., 2023).4 The findings showed that the higher dose yielded fewer active MRI lesions, indicating potential benefit beyond bone health. systematic review and meta-analysis: based on 32 reviews of clinical trials involving 8400 children who received high-dose vitamin D treatments ranging from 1200 to 10,000 IU per day, and bolus doses ranging from 30,000 IU per week to a single dose of 600,000 IU, found that no increased risk of serious adverse events was associated with high-dose vitamin D treatments (Brustad et al., 2022).5 Clearly: The healthcare system is focused on treating health problems, rather than preventing health problems. In all fairness though, I note that virtually no one goes to their doctor to learn how to prevent health problems — they go to their doctor to seek treatment for health problems. References 1. Johnson, D. A. (2025, May 20). The Overlooked Link Between Vitamin D and GI Health. Medscape, Retrieved from https://www.medscape.com/viewarticle/overlooked-link-between-vitamin-d-and-gi-health-2025a1000bki 2. Dan, L., Wang, S., Chen, X., Sun, Y. Fu, T., Deng, M., . . . Wang, X. (2024). Circulating 25-hydroxyvitamin D concentration can predict bowel resection risk among individuals with inflammatory bowel disease in a longitudinal cohort with 13 years of follow-up. International Journal of Surgery, [Published online]. Retrieved from https://journals.lww.com/international-journal-of-surgery/abstract/9900/circulating_25_hydroxyvitamin_d_concentration_can.1249.aspx 3. Burt, L. A., Billington, E. O., Rose, M. S., Raymond, D. A., Hanley, D. A., and Boyd, S. K. (2019). Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. JAMA, 322(8), pp 736–745, Retrieved from https://pubmed.ncbi.nlm.nih.gov/31454046/ 4. Cassard, S. D., Fitzgerald, K. C., Qian, P., Emrich, S. A., Azevedo, C. J., Goodman, A.D., . . . Mowry, E. M. (2023) High-dose vitamin D3 supplementation in relapsing-remitting multiple sclerosis: a randomised clinical trial. EClinicalMedicine, 13;59,101957. Retrieved from https://pubmed.ncbi.nlm.nih.gov/37125397/ 5. Brustad, N., Yousef, S., Stokholm, J., Bønnelykke, K., Bisgaard, H., and Chawes, B. L. (2022). Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years: A Systematic Review and Meta-analysis. JAMA Network Open, 5(4). e227410 Retrieved from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791031
|
AuthorWayne Persky Archives
March 2026
Categories |
Offices: 19242 Darrs Creek Rd, Bartlett, Texas 76511-4460
RSS Feed 
