This is a common symptom for both ME/CFS and Long COVID. This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does.

My default view is that this symptom is likely due to vesicular constriction/inflammation or “stick blood” (which contains many coagulation possibilities) resulting in low warming blood flow.

Study Populations:

Symptom	Reference	Study
Sleep: Unrefreshed Sleep	1087	78

• Bacteria Detected with z-score > 2.6: found 145 items, highest value was 12.6
• Enzymes Detected with z-score > 2.6: found 170 items, highest value was 5.3
• Compound Detected with z-score > 2.6: found No items

The highest z-scores above are more than most other symptoms. This indicates that the causes are more homogeneous bacteria shifts.

Interesting Significant Bacteria

All bacteria found significant had too low levels. The dominant genus is Prevotella with the P.Copri being usually 90% of the genus count in our reference, but only 14% of the genus count with Cold Extremities indicating that the shift is very species specific. Looking at Prevotella copri in isolation, we see the best documented ways of increasing it are: mediterranean diet, resveratrol (grape seed/polyphenols/red wine), berberine, navy bean,  Conjugated Linoleic Acid and linseed(flaxseed).

It is interesting to note that some of these are known to improve coagulation or reduces inflammation

• Therapeutic Potential of Resveratrol in COVID-19-Associated Hemostatic Disorders [2021]
• One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. [2012]
• Interaction between resveratrol and thrombin and its biological implication. [2011]
• Berberine alleviates myocardial ischemia-reperfusion injury by inhibiting inflammatory response and oxidative stress: the key function of miR-26b-5p-mediated PTGS2/MAPK signal transduction. [2022]
• Berberine as a natural modulator of inflammatory signaling pathways in the immune system: Focus on NF-κB, JAK/STAT, and MAPK signaling pathways. [2022]
• Dietary conjugated linoleic acid links reduced intestinal inflammation to amelioration of CNS autoimmunity. [2021]

Bacteria	Reference Mean	Study	Z-Score
Prevotella copri (species)	66900	3090	12.6
Prevotella (genus)	74698	21293	7.6
Prevotellaceae (family)	82172	36608	6.1
Bifidobacterium kashiwanohense PV20-2 (strain)	326	78	5.9
Bifidobacterium catenulatum subsp. kashiwanohense (subspecies)	317	78	5.8
Sporolactobacillaceae (family)	173	58	5.7
Thermosediminibacterales (order)	48	18	5.7
Sporolactobacillus (genus)	174	60	5.5
Sporolactobacillus putidus (species)	174	60	5.5
Bifidobacterium gallicum (species)	3784	783	5.5
Lactiplantibacillus pentosus (species)	123	22	5.3
Phocaeicola coprocola (species)	7584	663	5

Interesting Enzymes

Most (99%) enzymes found significant had too low levels.

Enzyme	Reference Mean	Study Mean	Z-Score
n/a (3.4.24.20)	40	16	5.3
2-acetylphloroglucinol C-acetyltransferase (2.3.1.272)	182	58	5.1
ATP:L-threonine O3-phosphotransferase (2.7.1.177)	2416	529	5

Bottom Line

In this study, one species shouts out as the cause by not being there Prevotella copri. I would really emphasis the items listed above as encouraging its growth.

It may be available “soon” as a probiotic, “The gut bacterium Prevotella copri (P. copri) has been shown to lower blood glucose levels in mice as well as in healthy humans, and is a promising candidate for a next generation probiotic aiming at prevention or treatment of obesity and type 2 diabetes.” [2021]

This article is an interesting read: The Strange Case of Prevotella copri: Dr. Jekyll or Mr. Hyde? Especially for those who think all bacteria can be classified as either good or bad.

In terms of retail probiotics suggested, the E.Coli probiotic, Symbioflor-2 is suggested.

The a priori suggestions, shown below, contains the items for P. Copri cited above.

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