EP.393/ What Are Lipopolysaccharides and What’s Their Role in Endometriosis Growth and Pain?
Today I want to talk about lipopolysaccharides and their role in endo growth and pain.
Lipopolysaccharides (known as LPS or endotoxins) are toxins that are released from gram-negative bacteria. LPS have been found at higher levels in the pelvic fluid and menstrual blood of people with endo, and trigger specific inflammatory pathways that further endo growth and pain.(1)
In fact, LPS are now thought to be an initial inflammatory mediator in endometriosis pathogenesis.(2)
So, where are these LPS coming from?
Elevated levels of e.coli, a gram negative bacteria, have been found in the gut microbiome, menstrual blood, vagina, cervical and endometrial samples of people with endo(3).
Researchers believe that the presence of e.coli is the cause of the high levels of LPS we see in the pelvic cavity of people with endo, as LPS “break off” e.coli bacteria.(4) They also think that translocation from the gut to the pelvis, is one of the key ways that e.coli and LPS are getting to this area.(4) Translocation of LPS is the movement through the gut barrier into the blood stream and rest of the body.(5)
So, why might this be happening in the endo population?
Many things can weaken the intestinal barrier, and this damage to the barrier lining is called increased intestinal permeability (leaky gut). Increased intestinal permeability can be caused by an unknown condition like coeliac disease, which damages the small intestine,(6) it can also come from food intolerances and sensitivities,(7) repeated NSAID use(8) and microbiome dysbiosis,(9) to name a few of the causes. All of these issues are common in the endo community.(10)
But another thing that causes intestinal permeability is SIBO, as SIBO increases LPS levels(11) due to the overgrowth of gram-negative bacteria like E.coli and Klebsiella, found in hydrogen SIBO.(12) The high levels of LPS are one of the main causes of the intestinal permeability seen in SIBO.
So, now let’s look at how LPS further endo growth.(13)
E. coli releases LPS
LPS binds to TLR4 (toll-like receptor 4) on immune cells (including mast cells).
TLR4 activation triggers the immune cells to release:
Cytokines, such as IL-1β, TNF-α, IL-6, which promote inflammation and cell proliferation
Chemokines, such as IL-8, MCP-1, which attract more immune cells to the pelvic environment
Growth factors, such as VEGF and TGF-𝛽, which support angiogenesis (blood vessel formation), fibrosis and lesion growth
PGE2, which enhances local inflammation, increases pain(14) and suppresses effective immune clearance. PgE2 also promotes e.coli growth by suppressing immune function that would otherwise target the bacteria, possibly creating a vicious cycle.(15)
TLR4 is essentially the trigger switch, and research found that this inflammatory cascade from LPS could be suppressed by blocking TLR4.(16)
So, how do we reduce e.coli, LPS and repair the gut barrier?
It’s a process, which is why I dedicate so much of my work to it, but you may have noticed a lot of my ‘how to’ type podcasts are focused on this, for example, PHGG inhibits e.coli, also helps to normalise the gut microbiome and increases butyrate, a short chain fatty acid us endo peeps are low in, which keeps the gut barrier healthy and intact.(17) I’ll link to that episode in the show notes.
Ultimately, whether you have dysbiosis or SIBO, the goal is to normalise your gut microbiome as much as possible, repair the gut barrier, and also try to calm the inflammatory immune reaction to LPS, which you can do with a number of tools and strategies, like a supplement called berberine.(18)
Throughout my podcasts I tend to highlight whether something helps with these issues, so listen out for those, but also, focus on improving your gut microbiome, whether that’s eating to support healthy bacteria (my recipes!) or more focused treatments like a SIBO protocol.
If you’re curious to learn more about restoring the microbiome and treating SIBO, I’ve linked to a few episodes in the show notes.(19)
References
1) https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1363455/full
2) Bacterial contamination hypothesis: a new concept in endometriosis - PMC, Evaluation of microecological therapy in endometriosis through modulation of the gut microbiota | European Journal of Medical Research
3) Bacterial contamination hypothesis: a new concept in endometriosis - PMC, Significant increased isolation of Escherichia coli in Iranian women with endometriosis: a case control – study - PMC, The bidirectional relationship between endometriosis and microbiome - PMC
4) Bacterial contamination hypothesis: a new concept in endometriosis - PMC, The process of microbial translocation - PubMed
5) https://pmc.ncbi.nlm.nih.gov/articles/PMC7033038/
6) https://link.springer.com/article/10.1007/s10620-005-2574-0
7) https://pubmed.ncbi.nlm.nih.gov/21070397/, https://www.frontiersin.org/journals/allergy/articles/10.3389/falgy.2024.1505834/full, https://pmc.ncbi.nlm.nih.gov/articles/PMC9101724/
8) https://pubmed.ncbi.nlm.nih.gov/19148789/
9) https://pmc.ncbi.nlm.nih.gov/articles/PMC10954893/, https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2024.1380713/full
10) https://celiac.org/2024/04/25/new-research-shows-higher-risk-of-reproductive-disorders-for-women-with-celiac-disease/, https://pmc.ncbi.nlm.nih.gov/articles/PMC3988867/, https://pmc.ncbi.nlm.nih.gov/articles/PMC12942269/, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2831953
11) https://pmc.ncbi.nlm.nih.gov/articles/PMC12030604/
12) Modern concepts of small intestinal bacterial overgrowth
13) https://link.springer.com/article/10.1186/s40001-025-03334-4, https://pmc.ncbi.nlm.nih.gov/articles/PMC11370979/, https://pmc.ncbi.nlm.nih.gov/articles/PMC5902457/, https://link.springer.com/article/10.1186/s40001-025-03334-4
14) https://pubmed.ncbi.nlm.nih.gov/20511671/
15) https://academic.oup.com/humrep/article-abstract/27/12/3417/652782
16) https://link.springer.com/article/10.1186/s40001-025-03334-4
17) https://www.theendobellycoach.com/podcast/phgg-endo-belly-sibo-ibs
18) https://pmc.ncbi.nlm.nih.gov/articles/PMC5740511/, https://pmc.ncbi.nlm.nih.gov/articles/PMC9645259/, https://www.mdpi.com/1422-0067/26/24/12021, https://www.imrpress.com/journal/FBL/31/1/10.31083/FBL45524
19) https://www.theendobellycoach.com/podcast/probiotics-for-sibo-treatment, https://www.theendobellycoach.com/podcast/sibo-endometriosis-and-interstitial-cystitis-connection-wth-dr-allison-siebecker, https://www.theendobellycoach.com/podcast/endo-belly-endometriosis-how-to-treat-sibo-ibs-allison-siebecker
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