Thread by @FZMarques

I'm super excited to share the results of our phase 2 randomised clinical trial using gut microbial metabolites to lower #bloodpressure, for now as a pre-print

@VicHeartInst @MonashBiol @Monash_Science @MonashUni

Funded by @heartfoundation @nhmrc

A 🧵

medrxiv.org/cgi/content/sh…

Work led by @HamdiAJama @dakotarrj in collaboration with many at @MonashUni and @BakerResearchAu inc @lab_nakai @RachelClimie @CreekLab @GeoffreyHead plus others not on Twitter

We started this work after our discovery in 2017 in mice that gut microbial metabolites explained the long-known association between high fibre intake and lower blood pressure and cardiovascular disease

We first tested acetate, published in @CircAHA

ahajournals.org/doi/full/10.11…

Subsequently, we tested all 3 gut microbial metabolites in mice

While acetate still had the best #bloodpressure lowering results, butyrate had an essential impact on the gut tissue itself, key for improving the gut epithelial barrier

@CircAHA

ahajournals.org/doi/10.1161/CI…

So we set on a combination of acetate + butyrate

However, mice receive these in their drinking water

We needed to find a way to deliver this to patients that i) tasted good to ensure compliance, and ii) resulted in slow, continuous release of acetate+butyrate

So we employed a new fibre supplement enriched for these metabolites, used by our collaborator Charles Mackay in @NatImmunol

This is important because the gut microbiota still ferments this fibre, resulting in the slow release of the metabolites

nature.com/articles/ni.37…

We designed a randomised, placebo-controlled, double-blind, cross-over phase 2 trial

Placebo controlling and double-blinding is a challenge for dietary studies, but we found a way by engaging with a research chef & dietitians

Participants ate the yummy chef-cooked meals 2x/day

We measured blood pressure using 24-hour monitoring, as well as home blood pressure, over a period of 3 weeks

Participants had 3 weeks off between study arms

Bloods and faecal samples were collected to measure levels of gut metabolites and microbiota

So what did we find?

Our intervention:
I) Increased levels of acetate and butyrate
II) Lowered 24-hour and central systolic blood pressure, with a clinically relevant effect
III) Changed the microbiota to produce even further microbial metabolites

This is exciting because:

I) We have been able to go from 2 experimental models to a clinical trial in 5 years - very rare in medicine!

II) Provides a new tool for hypertensive patients to lower their blood pressure

Check out our manuscript 🙂👆

@annetkiraboc1 @jenpluznick @BinaJoe4 @alta_schutte @phylogeo @LabTouyz @DrMarthaGulati @FadiCharchar @microbiome_net @MicrobiomeVIF @endocelldoc @dave_durgan @OzCvA @ISHBP @HBPRCA @CouncilonHTN @AHAMeetings @ISHR_AUS @MBmicrobiome @hmstaudacher

Check out our manuscript 🙂👆

@ChristofidouEvi @bykriscampbell @MicrobiomDigest @blink_e @gr_drummond @MarijaJelinic @mari_br_montrea @Matt_Snelson @MelindaCoughlan @Eli_melb