Butyrate low in ME/CFS - one possible reason

bertiedog

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It has been shown by several researchers - Dr Lipton comes to mind - that one of the most important Short Chain Fatty Acids (SCFAs) is low in ME and also in other inflammatory bowel conditions, diabetes and other chronic illnesses.

I belong to GeneticsLifehacks who give a weekly round up of various topics and one of the updated ones is on TNF alpha which is an inflammatory cytokine. I don't know if this has been shown to be high in ME, I haven't had time to check but my genetics were shown as follows -

rs1800629 - A/G, also A/A - higher TNF-alpha

Short-chain fatty acids, such as butyrate, are important for colon health. High levels of TNF-alpha decrease the expression of transporters for butyrate (reference supplied.
.
However, the two other SCFAs, acetate and propionate are at good levels in my stool tests so I wonder if this SNP could be the reason why my butyrate is always low despite eating the foods which are supposed to support its production?

I wonder if this SNP rs1800629 which is associated with higher TNF alpha is common in ME which would account for the low butyrate in our illness?

Pam
 

Wishful

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It's a possible hypothesis. However, there are plenty of other possibilities, such as microbes that consume butyrate (or its precursors without releasing butyrate). Maybe your gut conditions are such that they bias the bacteria that should produce butyrate to produce less.

Does that SNP affect the amount of TNF-alpha actually inside the gut microbiome? Are those 'transporters for butyrate' transporting it from inside bacterial cells to the outside (where it can be measured in stool samples) or are they transporting it across membranes elsewhere in the body? Many hypotheses involve misapplication of some finding, such as something that affects specific cells in one part of the body inappropriately being assumed to affect other cells elsewhere.
 

bertiedog

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I don't know if this has been shown to be high in ME
I have just checked this and there are indeed a few studies, mainly from Norway that do show high TNF alpha is high in ME/CFS.

Next year I am going to do another Biomesight stool test to see if I have been able to raise butyrate by having Bimuno which supplies GOS, daily as well as 5 gm FOS and adding more of the suggested foods to my diet since July of this year. One would hope that indeed this is the case but if not then there has to be other reasons for it to remain too low and not solely diet being involved.

Pam
 

bertiedog

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A bit more on what having higher than normal TNF alpha does to the body -

"Do you feel like you are always dealing with inflammation? Joint pain, food sensitivity, skin issues, gum disease, etc… It could be that your body is genetically geared towards a higher inflammatory response due to high TNF-alpha levels.

Tumor necrosis factor (TNF) is an inflammatory cytokine that acts as a signaling molecule in our immune system. In an acute inflammatory situation, TNF-alpha plays an essential role in protecting us, but genetically higher TNF-alpha levels are also linked to chronic inflammatory diseases." (from genetic lifehacks.com)

Here is the bit about how it can affect intestinal absorption -

Intestinal absorption is altered with high TNF-alpha:
Inflammation and high TNF-alpha levels in the intestines alter the ability to absorb nutrients.

For example:

  • High TNF-alpha levels decrease the receptor needed for the absorption of vitamin C (SLC23A1).[ref]
  • Short-chain fatty acids, such as butyrate, are important for colon health. High levels of TNF-alpha decrease the expression of transporters for butyrate (SLC5A8).[ref]
  • Phosphate absorption is decreased when TNF-alpha is high in the intestines. Low phosphate absorption can cause problems with teeth and bones.[ref]
The site goes on to say that there are several variants that can lead to more active TNF alpha levels, I have just quoted on above, the others being rs361525, rs1799964, rs1799724. ( I also have another variant on the last SNP).

I have got to finish now but in addition to the above there are variants on the TNF alpha transporter gene and I will try and post these later.

Pam
 

Wishful

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"Butyrate serves as primary fuel for the colonocytes". So, low levels in stools might mean that the colonocytes are consuming it at a faster rate than normal. As I understand it, elevated TNF alpha would decrease the flow of butyrate into those epithelial cells, resulting in elevated butyrate remaining in the stool.