5 Years to a Designer Bacterial Microbiome? My Money’s on Yes

My psychic powers are in overdrive after reading an article on Medical Express yesterday morning about research being presented at the upcoming American Chemical Society’s fall meeting.[i]  I truly believe this is the first step toward custom modeling of the human microbiome.

Obviously, diet will always come first, but facing facts, getting people to change their diets – no matter how dire the situation – is often like trying to move Mount Everest.  So while we stubbornly stick to our unhealthy habits, we, in the industrialized world, continue to slide into inflammatory illnesses at ever increasing rates.

Probiotics and prebiotics may also help, but ultimately, (and I wish I could say I believed differently, but I don’t), I believe we (as a society, I mean) are going to end up needing pharmaceutical options to revamp our altered microbiomes.  People like to just take the pill; everything else is too much work.  And to boot, there are many factors out of our control that also adversely affect our microbiomes, such as stress levels or pollution exposures.  As the lead researcher on this study, Dr. M. Reza Ghadiri, says, “If we all ate a healthy diet, exercised and didn’t age, we wouldn’t have problems with our gut microbiome and many diseases. But, that’s not how all people live.”

At the upcoming conference, Dr. Ghadiri and colleagues from The Scripps Research Institute are presenting work they recently conducted in which they created artificial peptides (short strings of amino acids – so basically little proteins) called self-assembling cyclic D, L-α-peptides.  These artificially created peptides target very specific pathogenic bacteria, and by inhibiting the growth of the organism, allow beneficial bacteria a competitive advantage.

Says Dr. Ghadiri:  “Our hypothesis was that instead of killing bacteria, if we could selectively modulate the growth of certain bacteria species in the gut microbiome using our peptides, more beneficial bacteria would grow to fill the niche, and the gut would be ‘remodeled’ into a healthful gut…”

He goes “Our theory was that process would prevent the onset or progression of certain chronic diseases.”

The scientists first tested their peptides in an in vitro mouse model.  They used a type (LDL receptor knockout mice) that have been bred to do well on low fat diets.  When fed a high fat “Western” diet, they rapidly develop extremely high levels of LDL (bad) cholesterol and within weeks, arterial plaques.  The researchers grew models of these mice microbiomes in their lab, tested several of the new peptides on them, and ended up selecting 2 that seemed the most effective for modulating the microbiomes to look more like those of healthy mice on low fat diets.

Their next step was an in vivo experiment in which they split this same type of mouse into 3 groups:  the first group was fed a low fat diet; a second group was fed a high-fat Western-type diet; and a third group was fed a high-fat diet plus one of the selected peptides. They then analyzed the mice’ microbiomes from fecal samples and also tracked immune markers, inflammation levels and the development of arterial plaques.  The mice on the peptides had a 50% reduction of plasma cholesterol as compared to the mice fed a high-fat diet not on the peptides, and no significant plaques formed in their arteries.  They also had markedly lower levels of inflammation as well as higher levels of regulatory cytokines (which modulate inflammation levels).  “These mice resembled those on a low-fat diet,” says Dr. Ghadiri.

The scientists hypothesize that the shift in gut bacteria affects genes that, in turn, affect bile acids (which digest fats), thus leading to changes in cholesterol levels.  They also believe the biome alterations may affect other genes related to the immune system and inflammatory processes.

By the way, the peptides are not digested and pass right through the animals.

The potential ramifications of this work are vast.  Firstly, if this ends up working in humans – which I can’t believe is far off – we may not only be able to easily sculpt an unhealthy microbiome to resemble those of healthy people (think about all the diseases now associated with altered bacterial microbiomes – from autism to obesity to autoimmune diseases to fibromyalgia/chronic fatigue to depression to Parkinson’s, etc.) but perhaps too, antibiotics may have to be used markedly less…not just in us, but in the food-animal markets.

Here is a link to a great 10 minute talk by Dr. Ghadiri from this past April on this topic.  It’s worth the few minutes of your time.  He actually gave me a serious LOL…so yeah…spend 10 minutes watching this.  (If I had $50 million, I’d lob it his way, believe me.)  He says we all need to hang on for 5 more years.

Believe me, I will be following this very closely.

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[i] https://medicalxpress.com/news/2019-08-remodeling-unhealthful-gut-microbiomes-disease.html

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