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Loved the interview with Dr. Jessey. Thanks so much. I will subscribe. I have loved your interviews with Geert Vanden Bossche, Dr. McMillan. You are a gem and a true humanitarian with a kind heart that shines through all your presentations. You deserve support. Thank you for supporting Geert. He is one of my pandemic heroes, no doubt. Cheers, sir. MStClair, Family Nurse Practitioner, ret.

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This can be explained by metformin impact on butyrate producing bacteria. When Rachel Jessey mentioned butyrate effect, this connected the dots with the presentation of Dr. Leo Galland who emphasised the depletion of Faecalibacterium prausnitzii, which is obligate anaerobe bacteria.

This suggests to increased colonocyte oxygenation during SARS-CoV-2 resulting in the shift from obligate anaerobes to facultative anaerobes, that is, from short chain fatty acid producing bacteria to more pathogenic bacteria.

According to Litvak et al 2018 colonocyte oxygenation during viral infection may result in 2 forms:

- because of neutrophil transepithelial migration, which leads to a depletion of Clostridia, thereby lowering the luminal concentration of short-chain fatty acids, such as butyrate, or/and

- because of increased metabolic requirements of the colonic epithelial cells to release pro-inflammatory cytokines. Since colonocytes must look for other sources of energy during high demanding circumstances, they end up pulling glucose from the bloodstream and fermenting it to lactate, a process that does not utilize oxygen. Such skewed metabolism is characterised by high lactate release, low oxygen consumption and elevated synthesis of iNOS, an enzyme that generates nitric oxide (NO). Conversion of nitric oxide into nitrate (NO3−) in the gut lumen together with oxygen (O2) provide electron acceptors that drive an expansion of facultative anaerobic bacteria.

This suggests to effective prevention and treatment of long covid with sufficient butyrate levels and gut microbiome dominated by obligate anaerobe bacteria.

Additionally, it is worth to mention observation described by CA Devaux et al 2021 that in the presence of vitamin D3, the vitamin D receptor expressed in enterocytes translocate to the nucleus where it ensures molecular processes resulting to the integrity of epithelial tight junctions. The same effect metformin has on the gut.

Therefore, butyrate and D3 levels are strong indicators of potential outcome for C19 and PASC upon exposure to SARS-CoV-2.

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