#MCMMs
💥Personalized C. difficile colonization risk prediction and probiotic therapy assessment in the human gut💥

I'm very excited about this work, driven by Alex Carr & co-supervised by @cdiener.com

@cp-cellsystems.bsky.social @isbscience.org @nitinbaliga.bsky.social

www.cell.com/cell-systems...

🧵...
Personalized Clostridioides difficile colonization risk prediction and probiotic therapy assessment in the human gut
Carr et al. show how microbial community-scale metabolic models (MCMMs) predict personalized Clostridioides difficile colonization risk and probiotic efficacy. MCMMs reveal key metabolic strategies ex...
www.cell.com
August 6, 2025 at 4:51 PM
Happy to team up with @microbe-enjoyer.bsky.social to highlight fantastic work by @gibbological.bsky.social, Alex Carr, and colleagues using community scale metabolic models to predict risk for C. difficile colonization!

See the initial study here: www.cell.com/cell-systems...
August 20, 2025 at 4:25 PM
Microbial community-scale metabolic models (MCMMs) map gut microbiome composition & dietary context to functional outputs, at scale.

Here, we describe these emerging tools & their utility to both basic & translational microbiome research. @natmicrobiol.nature.com

www.nature.com/articles/s41...
Moving from genome-scale to community-scale metabolic models for the human gut microbiome - Nature Microbiology
In this Perspective, Deiner, Gibbons and colleagues describe the current strengths and limitations of microbial community-scale metabolic models in microbiome research.
www.nature.com
April 11, 2025 at 2:38 PM
Postdocs in the lab Nick Quinn-Bohmann & Alex Carr, along with @cdiener.com, wrote a Perspective article on the challenges and opportunities posed by the rise of microbial community-scale metabolic models (MCMMs) in @natmicrobiol.nature.com

MCMMs are powerful tools! 💪

doi.org/10.1038/s415...
Moving from genome-scale to community-scale metabolic models for the human gut microbiome - Nature Microbiology
In this Perspective, Deiner, Gibbons and colleagues describe the current strengths and limitations of microbial community-scale metabolic models in microbiome research.
doi.org
December 19, 2025 at 12:06 AM
In July, Nick's precision nutrition paper was the cover article in Nature Microbiology (cover attached). Nick showed that microbial community-scale metabolic models (MCMMs) could be used to predict personalized SCFA production profiles in the context of a given dietary input doi.org/10.1038/s415...
December 18, 2024 at 5:35 PM
"We further demonstrate that MCMMs can predict personalized C. difficile growth suppression by a probiotic cocktail designed to replace fecal microbiota transplants (FMTs) for the treatment of recurrent CDI, and we identify new probiotic targets for future validation"

@gibbological.bsky.social 🤯
🦠 New paper out today in @cellpress.bsky.social's Cell Systems! ISB researchers show how personalized gut models can predict – and help prevent – dangerous C. diff infections before they strike.
Cell Systems paper: www.cell.com/cell-systems...
ISB news story: isbscience.org/news/health/...
August 6, 2025 at 4:18 PM
This was an exciting proof-of-concept that MCMMs can predict personalized probiotic engraftment in a real-world synbiotic trial.

We're excited to apply these models prospectively in precision nutrition trials, pending funds (LMK if you've got a million $$ burning a hole in your pocket!).
June 25, 2025 at 6:10 PM
🦠🔬🧫🧪🌍
Super cool use of metabolic models of reconstituted communities and inulin in a #synbiotic intervention to predict engraftment of specific strains in a clinical trial.

This is where #microbialEcology #ecoengineering should be going!

#SynComs #synbiotics #MCMMs
June 25, 2025 at 7:54 PM
Recently (in @cp-cellsystems.bsky.social), Alex Carr showed how MCMMs can predict personalized C. difficile colonization risk (the method can be adapted to other pathobionts).

Alex also showed how MCMMs can help with design of precision probiotics to block pathogens.

doi.org/10.1016/j.ce...
Redirecting
doi.org
December 19, 2025 at 12:06 AM
In prior work by Alex Carr, we've shown that we can predict engraftment/colonization probability for C. difficile in the context of an individual's microbiota, using MCMMs (this work is currently in press - stay tuned for that thread). www.biorxiv.org/content/10.1...
Personalized Clostridioides difficile engraftment risk prediction and probiotic therapy assessment in the human gut
Clostridioides difficile colonizes up to 30-40% of community-dwelling adults without causing disease. C. difficile infections (CDIs) are the leading cause of antibiotic-associated diarrhea in the U.S....
www.biorxiv.org
June 25, 2025 at 6:10 PM
In the trial, synbiotic supplementation significantly improved glucose control. We leveraged MCMMs to explore potential mechanisms: e.g., SCFA production. Indeed, we saw significant increases in butyrate with inulin supplementation, which increased further upon adding the probiotic taxa.
June 25, 2025 at 6:10 PM
Like I said up top, I'm really excited about the potential for microbial community-scale metabolic models (MCMMs) to predict pathobiont colonization risk & to design precision probiotic therapies that aim to prevent infections before they can start.

www.nature.com/articles/s41...
www.nature.com
August 6, 2025 at 4:51 PM
A new path forward for precision nutrition:

@BioBohmann, co-advised by @thaasophobia, used microbial community-scale metabolic models (MCMMs) to predict personalized short-chain fatty acid (SCFA) production profiles 🍌➕🦠🟰⚛️

https://doi.org/10.1038/s41564-024-01728-4...
November 13, 2024 at 8:03 AM
This is yet another demonstration of the clinical relevance of MCMMs for precision health and nutrition (gibbons.isbscience.org/publications/).

We hope to start testing these personalized, MCMM-designed interventions in prospective human trials in the next year.
Publications
Google Scholar Bold Underscored Text = Gibbons Lab members (starting in 2019); * = corresponding author; # = co-first author Patents Preprints Publications 2026 2025 2024 2023 2022 2021 2020
gibbons.isbscience.org
February 19, 2026 at 7:59 PM
We had a couple of preprints too:

1) Nick showed how MCMMs can predict probiotic engraftment and efficacy in thre human intervention trials...

www.medrxiv.org/content/10.1...
Metabolic modeling reveals determinants of prebiotic and probiotic treatment efficacy across two human intervention trials
Prebiotic, probiotic, and combined (synbiotic) interventions often show variable outcomes across individuals, driven by complex interactions between introduced biotics, the endogenous microbiota, and ...
www.medrxiv.org
December 19, 2025 at 12:06 AM
For the probiotic/biotherapeutic trials, we found that MCMMs predicted colonization/engraftment outcomes with 75-80% accuracy.

Empirical engraftment was assessed using qPCR or metagenomic sequencing. Model engraftment was defined as a predicted growth rate above a defined threshold.
February 19, 2026 at 7:59 PM
This preprint is our first proof-of-concept for how MCMMs can be leveraged to predict engraftment potential. There is no reason why this same approach couldn't be applied to any other pathobiont or probiotic taxon in the human gut, or to more complex interventions, like FMTs.
November 13, 2024 at 2:31 PM
MCMMs provide transparent, mechanistically-grounded predictions that should be fairly robust across human populations. As our genome-scale metabolic model databases improve, these MCMMs will only grow more powerful.
November 13, 2024 at 2:17 PM
We believe this work represents an advance in our ability to rationally predict personalized pathobiont colonization risk and assess efficacy of therapeutic probiotic interventions. Unlike more black-box machine learning approaches, MCMMs do not rely upon training data.
November 13, 2024 at 2:03 PM
Finally, as a proof-of-concept, we re-constructed a 6-member probiotic cocktail (i.e., a subset of VE303, with available metabolic models @VedantaBio; https://jamanetwork.com/journals/jama/fullarticle/2803996), which was able to protect most MCMMs from C. diff invasion in silico.
November 13, 2024 at 1:22 PM
Previously, C. diff recurrence risk was observed to be higher in low-diversity microbiomes (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684761/). We saw this in our MCMMs too, & we found that engraftment risk also increased at the top-end of the diversity spectrum. Risk was lowest...
November 13, 2024 at 12:52 PM
And MCMMs reveal taxa that cross-feed C. diff, like several of the butyrate-producing Clostridia, which appear to export succinate. Similarly, these cooperative interactions can vary a lot from person-to-person, even for the same bugs, highlighting the need for a systems approach
November 13, 2024 at 12:15 PM
MCMMs provide us with insight into potential competitors with C. diff, who import metabolites that it uses, like in the case of Phocaeicola and succinate (below). Even within the same taxon, these competitive interactions can vary a lot across individuals.
November 13, 2024 at 12:02 PM
Finally, we wanted to demonstrate the potential power of MCMMs to design and test (in slico) personalized dietary, prebiotic, and probiotic interventions that optimize individual-specific SCFA profiles.
November 13, 2024 at 11:36 AM