As usual from you, very fascinating and plausible-sounding hypothesis, though my expectations are tempered by the fact that in general most hypotheses don't end up panning out. Hoping for the best, though. Please let us know whether your predictions about her elevated Enterococcus (and about treating it) end up being right or wrong. As always, the best way to test these things are to see whether the predictions are accurate.
Loving this detective work you are doing. Is there any hint that smaller populations of microbes outside of the gut/mucosa might be having more direct impacts on various tissues and organs during disease states? Recent reports on the brain and tumour microbiomes has me wondering...
The main takeaway I keep getting from your posts is to just be super cautious around antibiotics, mostly via not ever needing them in the first place. Health Is Wealth looks different once you realize the long, long, long tail of things that might go horribly wrong in the hospital...better not to risk it in the first place. At least not until we get mass market probiotics that actually do anything worth a damn / FMT within the medical Overton Windows 11.
Did end up having a fun conversation with a customer the other day who was big mad about us being sold out of organic potatoes. "Root vegetables soak up pesticides, the regular ones are basically poison!" Not sure if she knew the specific glyphosate connection, or just coming from more general crunchy-hippie priors, but it was nice to see someone buying organic for the actual main plausible benefit rather than mood affiliation or rEgEnErAtIvE fArMiNg or whatever.
>The main takeaway I keep getting from your posts is to just be super cautious around antibiotics
You got it. I mean, imagine I was like "here's a pill that'll make your sore throat go away, and has a 10% chance of deleting a random protein-coding gene from your genome". You wouldn't take it! At least, hopefully
This is funny to read due to currently having a sudden sore throat and being rather irritated about it...if it meant not missing tomorrow's (bonus pay) shift, I'd definitely pay a decently high "price"!
Do you actually have a generalized percentage for the odds of rolling a Critical Failure on antibiotics? Obviously there's some times when it'd be very stupid not to take them, so whatever, but the correct amount of gambling on right-tail outcomes in non-emergencies is definitely not zero either.
I don't have a generalized percentage because the odds are different for each (type of antibiotic) x (condition) combo.
I pulled out 10% as an example, because 6 of the 51 people in Midtvedt et al (1990) fully lost their fecal coprostanol after a standard 6d course of antibiotics, but--because coprostanol production is restricted to Acutalibacteraceae, which are gram-positive bacteria--antibiotics that target gram-positive organisms were way worse for that function. The researchers assigned 6-7 subjects to each group, and by the end of the study two people in the vancomycin group and three in the erythromycin group had zero coprostanol five weeks later. so 5 out of 12-14.
But in Norgaard et al, the Danish study I pulled from for the MS post, they had 3259 patients out of a national population of 5.3M, implying a general risk of MS in their population of .06%.
Take nitrofurantoin, which was associated with an odds ratio of 1.83, and that risk goes up to 0.1%. Macrolides had an odds ratio of 1.31, so that would just take you up to 0.78%.
So we basically have to build out a Wild Magic Table for each antibiotic, like:
Nitrofurantoin: Roll a D1000.
-If the result is 1, you contract multiple sclerosis. Roll to see whether it's primary-progressive or relapsing-remitting.
-If the result is below 350, you lose your coprostanol pathway. After 100 cumulative days in this state, you must begin each day with a constitution saving throw, DC 3. If you fail, you die of a sudden cardiac event.
-If the result is divisible by 100, you enter psychosis. Does it stick around? Roll to find out!
...and so on.
Honestly this WOULD be a super useful chart to have...
Hard to say! There's a possibility, even in this model. Consider: Enterococcus wouldn't produce H2O2 unless it had a degree if resistance to its toxic effects. So it's possible that having a gain-of-function mutant superoxide dismutase, like in familial ALS, makes it easier for H2O2 producers to take over the microbiome. DM me, we'll get em sequenced
Great work. There is a group of Docs having good success with ALS and gut health is part of it. There is a conference in Vegas in October that is run by the patient foundation that started the ball rolling. I will share this with a person I know who is connected. Also, I happen to be on an airplane and never brought with me the comprehensive source book of bacterial protein toxins. 😂 enterococcus toxins have only one reference in the book to intracellularly, active bacterial protein toxins, and the two pages referenced are discussing Colibactin. Usually in a cola, but as we both know, there is horizontal Gene transfer like mad in the gut.
Some voice to text typos. Anyway. Brought the book with me. And it’s usually in Ecoli but…looks like there is a pks island in both EColi and E faecalis
As usual from you, very fascinating and plausible-sounding hypothesis, though my expectations are tempered by the fact that in general most hypotheses don't end up panning out. Hoping for the best, though. Please let us know whether your predictions about her elevated Enterococcus (and about treating it) end up being right or wrong. As always, the best way to test these things are to see whether the predictions are accurate.
Loving this detective work you are doing. Is there any hint that smaller populations of microbes outside of the gut/mucosa might be having more direct impacts on various tissues and organs during disease states? Recent reports on the brain and tumour microbiomes has me wondering...
The main takeaway I keep getting from your posts is to just be super cautious around antibiotics, mostly via not ever needing them in the first place. Health Is Wealth looks different once you realize the long, long, long tail of things that might go horribly wrong in the hospital...better not to risk it in the first place. At least not until we get mass market probiotics that actually do anything worth a damn / FMT within the medical Overton Windows 11.
Did end up having a fun conversation with a customer the other day who was big mad about us being sold out of organic potatoes. "Root vegetables soak up pesticides, the regular ones are basically poison!" Not sure if she knew the specific glyphosate connection, or just coming from more general crunchy-hippie priors, but it was nice to see someone buying organic for the actual main plausible benefit rather than mood affiliation or rEgEnErAtIvE fArMiNg or whatever.
>The main takeaway I keep getting from your posts is to just be super cautious around antibiotics
You got it. I mean, imagine I was like "here's a pill that'll make your sore throat go away, and has a 10% chance of deleting a random protein-coding gene from your genome". You wouldn't take it! At least, hopefully
This is funny to read due to currently having a sudden sore throat and being rather irritated about it...if it meant not missing tomorrow's (bonus pay) shift, I'd definitely pay a decently high "price"!
Do you actually have a generalized percentage for the odds of rolling a Critical Failure on antibiotics? Obviously there's some times when it'd be very stupid not to take them, so whatever, but the correct amount of gambling on right-tail outcomes in non-emergencies is definitely not zero either.
I don't have a generalized percentage because the odds are different for each (type of antibiotic) x (condition) combo.
I pulled out 10% as an example, because 6 of the 51 people in Midtvedt et al (1990) fully lost their fecal coprostanol after a standard 6d course of antibiotics, but--because coprostanol production is restricted to Acutalibacteraceae, which are gram-positive bacteria--antibiotics that target gram-positive organisms were way worse for that function. The researchers assigned 6-7 subjects to each group, and by the end of the study two people in the vancomycin group and three in the erythromycin group had zero coprostanol five weeks later. so 5 out of 12-14.
But in Norgaard et al, the Danish study I pulled from for the MS post, they had 3259 patients out of a national population of 5.3M, implying a general risk of MS in their population of .06%.
Take nitrofurantoin, which was associated with an odds ratio of 1.83, and that risk goes up to 0.1%. Macrolides had an odds ratio of 1.31, so that would just take you up to 0.78%.
So we basically have to build out a Wild Magic Table for each antibiotic, like:
Nitrofurantoin: Roll a D1000.
-If the result is 1, you contract multiple sclerosis. Roll to see whether it's primary-progressive or relapsing-remitting.
-If the result is below 350, you lose your coprostanol pathway. After 100 cumulative days in this state, you must begin each day with a constitution saving throw, DC 3. If you fail, you die of a sudden cardiac event.
-If the result is divisible by 100, you enter psychosis. Does it stick around? Roll to find out!
...and so on.
Honestly this WOULD be a super useful chart to have...
Do you theorize that in cases of familial ALS, gut micro biome has nothing to do with the triggering of the disease?
Hard to say, not knowing much about ALS. In the familial form, does it always tend to hit around the same age?
Im just trying to figure out if my PALS, who has familial ALS, should pursue the fecal transplant option.
We’ve had a suspicion that maybe his gut was related to the triggering of his ALS at age 37 because he’s had some curious food reactions.
But after reading your post, I’m wondering if it’s worth pursuing because you theorize that maybe jut sporadic ALS has a gut component.
Hard to say! There's a possibility, even in this model. Consider: Enterococcus wouldn't produce H2O2 unless it had a degree if resistance to its toxic effects. So it's possible that having a gain-of-function mutant superoxide dismutase, like in familial ALS, makes it easier for H2O2 producers to take over the microbiome. DM me, we'll get em sequenced
Great work. There is a group of Docs having good success with ALS and gut health is part of it. There is a conference in Vegas in October that is run by the patient foundation that started the ball rolling. I will share this with a person I know who is connected. Also, I happen to be on an airplane and never brought with me the comprehensive source book of bacterial protein toxins. 😂 enterococcus toxins have only one reference in the book to intracellularly, active bacterial protein toxins, and the two pages referenced are discussing Colibactin. Usually in a cola, but as we both know, there is horizontal Gene transfer like mad in the gut.
Some voice to text typos. Anyway. Brought the book with me. And it’s usually in Ecoli but…looks like there is a pks island in both EColi and E faecalis