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# Branches and ecological states of the gut microbiome: Mapping for future personalized nutritional and therapeutic interventions

Julien Tap

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Julien Tap. Branches and ecological states of the gut microbiome: Mapping for future personalized nutritional and therapeutic interventions. Journées Polepharma de Microbiomique, Polepharma, Nov 2023, Rouen, France. [hal-04316201](https://hal.inrae.fr/hal-04316201)

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https://hal.inrae.fr/hal-04316201

Submitted on 30 Nov 2023

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Distributed under a Creative Commons Attribution 4.0 International License
> Branches and ecological states of the gut microbiome:

# Mapping for future personalized nutritional and therapeutic interventions

Julien Tap

INRAE MICALIS

Journées Polepharma de Microbiomique- Rouen 2023

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> Different factors shapes the human gut microbiome

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> Diet and lifestyle effect host microbiome symbiosis

Are we uncoupling our
metagenome and our
genome?

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> Gut microbiome throughout life span

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Micobiota
Abundance &
diversity

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Factors
Influencing
the microbiota

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> Microbiome states resilience as key factor

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Healthy state

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Resistance

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Recovery

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Resilience

Healthy state

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Degraded state

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> Several attempts to decipher the microbiome structure

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Arumugam, Raes et al (2010)

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Costea et al (2017)

Dirichlet Multinomial Mixture (DMM) modeling

Limits:

Few association with diet

Few stability assessment (e.g. with time-series)

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> 35,000 human gut microbiome samples analyzed

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New computational method that help observe **global and local structure** at the same time

Time-series analysis to detect microbiome states

Region of birth, Lifestyle, diet, and health modelization

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> Human Gut microbiome structured as branches

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« Healthy index »

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Alpha-diversity

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« Aerobiosis »
> Low-diversity tips of branches display functional shifts

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amino acid catabolism increase
in *Bacteroides* branch tip

oxidative stress response increase
in *Prevotella* branch tip

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> Altered states showed functional differences within species

400 B. bifidum MAGS
phylogenomics

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*Bifidobacterium bifidum* strains may be enriched in phage-related genes in subjects with altered gut microbiomes states
> Dynamics between partitions are associated to branches

827 participants

2,998 samples

2,171 time-pairs

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Faecalibacterium/Bacteroides as a tipping element
explaining the switch between some states
> Gut microbiome alternative stable states hypothesis

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> Branches help to monitor gut microbiome recovery

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AMERICAN
GUT PROJECT
> Gut microbiome states are differentially associated with host and env factors

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Sex, exercises frequency and **region of birth** associated differentially between branches

Lifestyle and hygiene associated with altered state within *Bacteroides* branch

Specialized diet associated with altered state within *Prevotella* branch
> Do we already observe a intergenerationally mass extinction ?

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> Probiotics engraftment are gut microbiome baseline dependent

Modular coalescence between gut and biotics species

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"Engraftment" as function of existing niche and metabolic pathway

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> Probiotics clinical effect is gut microbiome baseline dependent

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flatulogenic diet (61% carbohydrates, 25% proteins and 14% fat, 27 g of fiber per day)

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After FMP consumption, FMP active strains detected by metatranscriptomics

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c

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After FMP intake (TP5), higher responder group showed higher methanogenesis activity than low-responders

INRAE
> Endgame : From gut microbiome states to next-gen biotics

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INRAE

Branches and ecological states of the gut microbiome

22.11.23 / Julien Tap / fme.micalis.fr

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Trends in Microbiology

Prevent gut microbiome critical transition to strengthen its resilience using next-gen biotics
> Towards selecting strains with abilities to prevent tipping point in gut microbiota

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Increase of peptidoglycan levels for cell wall formation *F.prau*

Lebas, Derrien and colleagues (2020)

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INRAE
> Take home messages

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* Gut microbiome ecological landscape is made of **local states** that are dynamically linked within "**branches**" where **critical transition** occurred

* Biotics can help but **effects may be personalized** thank to gut **microbiota states at baseline**

* Prototyping next-gen biotics should **include gut tipping elements** during screening for better **personalized and beneficial effects**.

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> Acknowledgments

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UC San Diego

Rob Knight's lab
Daniel McDonald
Franck Lejzerowicz
...

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DANONE
NUTRICIA
RESEARCH

Muriel Derrien
Patrick Veiga
Boris Le Nevé
...

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Vall d'Hebron
Institut de Recerca

Chays Mannichanh
Fernando Azpiroz
Iñigo Oyarzun
...

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INRAO

Branches and ecological states of the gut microbiome - Journées Polepharma de Microbiomique - Rouen 2023

22.11.23 / Julien Tap / fme.micalis.fr