[GUEST ACCESS MODE: Data is scrambled or limited to provide examples. Make requests using your API key to unlock full data. Check https://lunarcrush.ai/auth for authentication information.]  Greg Mushen [@gregmushen](/creator/twitter/gregmushen) on x 24.2K followers Created: 2025-07-26 15:37:18 UTC Yes. Although, with some important distinctions. Also, I absolutely share your frustration with microbiome research. Butyrate production is extremely important in the colon for many reasons, but one of the top reasons is it supplies ~70% of ATP to the colonocytes. Butyrate is mainly produced by saccharolytic bacteria in the colon. They ferment fiber to butyrate, acetate, and propionate. SCFA is acidic, so the production or lack thereof is the primary driver of colonic pH. pH is the driver of what genera live and which ones dominate. In higher pH, proteolytic genera are favored, and in the instance of a lower fiber diet, SCFA production can collapse (60-70%), and SCFA production shifts source. The two main sources are fermentation from mucin (via akkermansia, etc.), and BCFA production via proteolytic fermentation. The issue with mucin fermentation is substrate availability since only about 3g daily is available which means total SCFA production is rate-limited. Mucin fermentation is biased toward acetate which means that colonocytes may not have enough ATP available (since butyrate provides this), nor enough FFAR2 signaling since colonocytes preferentially bind butyrate. Proteolytic genera can ferment amino acids to BCFA which are chemically similar to SCFA (basically in iso form), but they have a weaker binding affinity than the non-iso forms. Now…to my own personal set of frustration with microbiome research. First is the use of is the use of PIRCUSt. While it can detect the presence of taxa, and the model has the functional routes of these taxa, the model has not the greatest accuracy, precision or F1 scores. This leads to conclusions that I feel are not warranted, such as the presence of saccharolytic genera suggesting no change on a meat-based diet. The problem with this is while those genera are absolutely present, it does not mean they are functional. They could be present, but mostly dormant. But the model doesn’t measure the functional output of these genera but rather assumes function since the presence of those genera is correlated with function. Secondly is the frequent use of fecal SCFA measurement for comparison. I can understand why they do this, but the measurement is sub standard. Around XX% of SCFA is absorbed before reaching the colon. Butyrate is used by the colonocytes, propionate is taken up by the liver, and acetate circulates. So comparing fecal samples of SCFA via fecal matter only and claiming they are identical is not giving us clear resolution into the functional differences.  XXX engagements  **Related Topics** [bacteria](/topic/bacteria) [colon](/topic/colon) [greg](/topic/greg) [Post Link](https://x.com/gregmushen/status/1949131922548093175)
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Greg Mushen @gregmushen on x 24.2K followers
Created: 2025-07-26 15:37:18 UTC
Yes. Although, with some important distinctions. Also, I absolutely share your frustration with microbiome research.
Butyrate production is extremely important in the colon for many reasons, but one of the top reasons is it supplies ~70% of ATP to the colonocytes.
Butyrate is mainly produced by saccharolytic bacteria in the colon. They ferment fiber to butyrate, acetate, and propionate.
SCFA is acidic, so the production or lack thereof is the primary driver of colonic pH. pH is the driver of what genera live and which ones dominate.
In higher pH, proteolytic genera are favored, and in the instance of a lower fiber diet, SCFA production can collapse (60-70%), and SCFA production shifts source.
The two main sources are fermentation from mucin (via akkermansia, etc.), and BCFA production via proteolytic fermentation.
The issue with mucin fermentation is substrate availability since only about 3g daily is available which means total SCFA production is rate-limited. Mucin fermentation is biased toward acetate which means that colonocytes may not have enough ATP available (since butyrate provides this), nor enough FFAR2 signaling since colonocytes preferentially bind butyrate.
Proteolytic genera can ferment amino acids to BCFA which are chemically similar to SCFA (basically in iso form), but they have a weaker binding affinity than the non-iso forms.
Now…to my own personal set of frustration with microbiome research.
First is the use of is the use of PIRCUSt. While it can detect the presence of taxa, and the model has the functional routes of these taxa, the model has not the greatest accuracy, precision or F1 scores.
This leads to conclusions that I feel are not warranted, such as the presence of saccharolytic genera suggesting no change on a meat-based diet. The problem with this is while those genera are absolutely present, it does not mean they are functional. They could be present, but mostly dormant. But the model doesn’t measure the functional output of these genera but rather assumes function since the presence of those genera is correlated with function.
Secondly is the frequent use of fecal SCFA measurement for comparison. I can understand why they do this, but the measurement is sub standard. Around XX% of SCFA is absorbed before reaching the colon. Butyrate is used by the colonocytes, propionate is taken up by the liver, and acetate circulates. So comparing fecal samples of SCFA via fecal matter only and claiming they are identical is not giving us clear resolution into the functional differences.
XXX engagements
