Chris Stewart
@stewartlab.bsky.social
Professor of Human Microbiome Research at Newcastle University.
Using 'omics and organoids to study diet-microbe-host interaction.
Microbiome; Microbiology; preterm infant; necrotising enterocolitis; inflammatory bowel disease; cancer.
He/Him
Using 'omics and organoids to study diet-microbe-host interaction.
Microbiome; Microbiology; preterm infant; necrotising enterocolitis; inflammatory bowel disease; cancer.
He/Him
Main take-homes:
1) Clostridium lacking pfoA toxin may be beneficial to preterm health as a probiotic or postbiotic
2) Where infants are potentially colonised with pathogenic pfoA+ C. perf, these results caution against widespread HMO supplementation (e.g., of formula milk)
1) Clostridium lacking pfoA toxin may be beneficial to preterm health as a probiotic or postbiotic
2) Where infants are potentially colonised with pathogenic pfoA+ C. perf, these results caution against widespread HMO supplementation (e.g., of formula milk)
January 28, 2025 at 11:36 AM
Main take-homes:
1) Clostridium lacking pfoA toxin may be beneficial to preterm health as a probiotic or postbiotic
2) Where infants are potentially colonised with pathogenic pfoA+ C. perf, these results caution against widespread HMO supplementation (e.g., of formula milk)
1) Clostridium lacking pfoA toxin may be beneficial to preterm health as a probiotic or postbiotic
2) Where infants are potentially colonised with pathogenic pfoA+ C. perf, these results caution against widespread HMO supplementation (e.g., of formula milk)
This work is only possible because of the amazing clinical team in Newcastle RVI. The Sanger team for the genome work. The whole of my team at @newcastleuni.bsky.social team for driving. And @wellcometrust.bsky.social and the Lister Institute for funding.
January 28, 2025 at 11:36 AM
This work is only possible because of the amazing clinical team in Newcastle RVI. The Sanger team for the genome work. The whole of my team at @newcastleuni.bsky.social team for driving. And @wellcometrust.bsky.social and the Lister Institute for funding.
There is lots more in the preprint so please do take a look. Any feedback is greatly appreciated!
January 28, 2025 at 11:36 AM
There is lots more in the preprint so please do take a look. Any feedback is greatly appreciated!
Given pfoA+ C. perf damages the epithelum, we explored competitive exclusion using live organoid co-culture. This revealed that pre-culture with pfoA- C. perf protects the preterm gut against pathogenic pfoA+ C. perf.
January 28, 2025 at 11:36 AM
Given pfoA+ C. perf damages the epithelum, we explored competitive exclusion using live organoid co-culture. This revealed that pre-culture with pfoA- C. perf protects the preterm gut against pathogenic pfoA+ C. perf.
We found that generally the CFS from pfoA- C. perf could suppress the pro-inflammatory response in stimulated organoids. There was also no adverse impacts on inflammation from this CFS.
January 28, 2025 at 11:36 AM
We found that generally the CFS from pfoA- C. perf could suppress the pro-inflammatory response in stimulated organoids. There was also no adverse impacts on inflammation from this CFS.
This is all very exciting for a potential therapy, but not if it negatively impacts the host. To study this we used preterm intestinal organoids and the recently developed co-culture system that accurately recapitulates O2 levels across the epithelium
January 28, 2025 at 11:36 AM
This is all very exciting for a potential therapy, but not if it negatively impacts the host. To study this we used preterm intestinal organoids and the recently developed co-culture system that accurately recapitulates O2 levels across the epithelium
... but promoted the growth of naturally occurring infant B. breve and B. longum (though not probiotic derived B. infantis). Because the CFS was harvested after growth on glucose, this is not explained purely by cross-feeding of LNT and other HMO degradation products
January 28, 2025 at 11:36 AM
... but promoted the growth of naturally occurring infant B. breve and B. longum (though not probiotic derived B. infantis). Because the CFS was harvested after growth on glucose, this is not explained purely by cross-feeding of LNT and other HMO degradation products
Now we wanted to see what impact cell free supernatant (CFS) from C. perf would have on infant gut microbiome development. Jon Chapman found it inhibited the growth of preterm infant pathobionts...
January 28, 2025 at 11:36 AM
Now we wanted to see what impact cell free supernatant (CFS) from C. perf would have on infant gut microbiome development. Jon Chapman found it inhibited the growth of preterm infant pathobionts...
Side step into some biochemistry - We found C. perf is able to use the sialic acid from DSLNT, but generally can not use LNT, which it "cross-feeds" to Bifidobacterium. The full digestion of DSLNT by C. perf was possible only when the β 1-3 bond was cleaved first.
January 28, 2025 at 11:36 AM
Side step into some biochemistry - We found C. perf is able to use the sialic acid from DSLNT, but generally can not use LNT, which it "cross-feeds" to Bifidobacterium. The full digestion of DSLNT by C. perf was possible only when the β 1-3 bond was cleaved first.
We therefore focused on a pfoA- C. perf isolate for further investigation, owing to it being in the hypovirulent linage V, lacking the pfoA toxin gene, its ability to use health-associated DSLNT, and its production of several beneficial SCFAs and metabolites
January 28, 2025 at 11:36 AM
We therefore focused on a pfoA- C. perf isolate for further investigation, owing to it being in the hypovirulent linage V, lacking the pfoA toxin gene, its ability to use health-associated DSLNT, and its production of several beneficial SCFAs and metabolites