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ForumsSemaglutide (Ozempic / Wegovy)Semaglutide and gut microbiome changes — looking for input

Semaglutide and gut microbiome changes — looking for input

NurseAsh_DET Wed, Sep 11, 2024 at 11:07 PM 41 replies 2,544 viewsPage 1 of 9
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NurseAsh_DET
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Sep 2024
Detroit, MI
Sep 11, 2024 at 11:07 PM#1

Alright nerds, this one's for you. I'm a microbiome researcher at a mid-tier R1 and I've been running 16S rRNA sequencing on my own stool samples since before I started semaglutide (n=1, I know, I know). But the data is genuinely interesting.

Background: 16S ribosomal RNA gene sequencing lets you profile which bacterial taxa are present in a fecal sample and in what relative abundance. I used the V3-V4 hypervariable region, Illumina MiSeq, QIIME2 pipeline, Silva 138 database.

I collected baseline samples (3 samples over 2 weeks pre-sema), then monthly samples for 6 months on Ozempic (titrated 0.25 → 0.5 → 1.0 → 2.0mg).

Key findings:

MetricBaselineMonth 3Month 6
Shannon Diversity3.823.413.67
Firmicutes:Bacteroidetes ratio2.8:11.9:11.6:1
Akkermansia muciniphila (%)0.3%1.8%4.2%
Prevotella copri (%)8.1%3.4%2.1%
Bifidobacterium spp. (%)2.4%5.7%6.1%

The Akkermansia bloom is the standout. A. muciniphila is consistently associated with improved metabolic health, better glucose tolerance, and reduced inflammation in the literature.[1] A 14x increase in 6 months is substantial.

The F:B ratio decrease tracks with weight loss — higher F:B ratios are associated with obesity in most (though not all) studies.[2]

Important caveats: my diet changed significantly (less processed food, more fiber, smaller portions). So I CANNOT attribute this to semaglutide directly vs. dietary changes. This is a confounder I can't resolve with n=1.

Anyone else tracking their microbiome on GLP-1 agonists? Has anyone seen published data on this?

[1] Depommier C, Everard A, Druart C, et al. "Supplementation with Akkermansia muciniphila in overweight and obese human volunteers." Nat Med. 2019;25(7):1096-1103.
[2] Ley RE, Turnbaugh PJ, Klein S, Gordon JI. "Human gut microbes associated with obesity." Nature. 2006;444(7122):1022-1023.
31 1FDA_TrackerJim, ricardo_MIA, BrianDallas92 and 28 others
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Dr.SurgeonPGH
Senior Member
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Mar 2024
Pittsburgh, PA
Sep 11, 2024 at 11:13 PM#2

This is incredible content. Exactly why I come to this forum instead of Reddit.

I've been using Viome (so metabolomics, not 16S) and while the methodology is different, my trends align with yours. My "gut health" score went from 42 to 71 over 8 months on sema. They specifically flagged increased butyrate-producing bacteria, which tracks with your Bifidobacterium increase.

Question: did you notice any GI symptom correlation with the diversity dip at month 3? My worst constipation was around months 2-4 and I've always wondered if there's a microbiome disruption phase.

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Dr.ReproEndo
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Jan 2024
Scottsdale, AZ
Sep 11, 2024 at 11:19 PM#3

Great question. Yes — months 2-3 were my worst for constipation and nausea, which is exactly when Shannon diversity bottomed out. The diversity recovery from month 3 to 6 was concurrent with GI symptom resolution. I don't think that's coincidental.

There's a 2023 paper from Peking University that looked at liraglutide (same GLP-1 class) in mice and found a transient dysbiosis phase followed by a "new equilibrium" with higher Akkermansia and Lactobacillus populations.[3] My data loosely mirrors that trajectory.

The mechanism is probably multifactorial — delayed gastric emptying changes substrate availability for gut bacteria, altered bile acid metabolism, reduced caloric intake shifting fermentation patterns, and possibly direct GLP-1 receptor signaling in the gut epithelium affecting mucus production (which would explain the Akkermansia bloom since it's a mucin specialist).

[3] Zhang Z, et al. "GLP-1 receptor agonists remodel gut microbiota in diet-induced obese mice." Gut Microbes. 2023;15(1):2208504.
29 24Dr.EndoEP, GraceAZ_72, carl_compliance and 26 others
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LindaRN_retired
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Dec 2024
Sarasota, FL
Sep 11, 2024 at 11:25 PM#4

ok this is way over my head scientifically but I just want to say my digestion is WILDLY different 7 months into sema. I used to have IBS-D symptoms almost daily and now I'm having like... normal poops? For the first time in years?

Is that consistent with what you're seeing in the data?

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Dr.EndoEP
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Oct 2024
El Paso, TX
Sep 11, 2024 at 11:58 PM#5

Absolutely. Improved F:B ratio and increased Bifidobacterium and Akkermansia are all associated with reduced intestinal permeability ("leaky gut") and reduced low-grade inflammation. Both of those are implicated in IBS pathology. Your symptom improvement is biologically plausible.

That said — delayed GI transit from GLP-1 agonism alone could also resolve IBS-D symptoms independently of microbiome changes. Probably both are contributing.

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