# Next-Gen Fermented Food: Harnessing Gut Microbiome Diversity and Functions

Julien Tap

► To cite this version:

Julien Tap. Next-Gen Fermented Food: Harnessing Gut Microbiome Diversity and Functions. 14th International Symposium on Lactic Acid Bacteria, Aug 2023, Egmond aan Zee, Netherlands. hal-04195035

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https://hal.inrae.fr/hal-04195035

Submitted on 4 Sep 2023

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Distributed under a Creative Commons Attribution 4.0 International License
> Next-Gen Fermented Food:
Harnessing Gut Microbiome
Diversity and Functions

Julien Tap

INRAE MICALIS

LAB Symposium 2023 - Egmond aan Zee

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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?

<figure><img src="image_5.png" /></figure>
> Gut microbiome throughout life span

<figure><img src="image_6.png" /></figure>

Micobiota
Abundance &
diversity

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Factors
Influencing
the microbiota

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> Gut Microbiome diversity associated with the region of birth during the lifespan

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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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> Dynamics between partitions are associated to branches

827 participants

2,998 samples

2,171 time-pairs

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<figure><img src="image_33.png" /><figcaption>d</figcaption></figure>

<figure><img src="image_34.png" /><figcaption>e</figcaption></figure>

<figure><img src="image_35.png" /><figcaption>f</figcaption></figure>

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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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> 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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> Harnessing the microbial potential of fermented foods to avoid the point of no return

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> How fermented foods can fit precision nutrition for health?

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Fermented foods valuable solution in
countering the decreased microbiome
diversity

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Personalized immune as function of gut
microbiota baseline

Wastyk et al., 2021

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> Large intersection between food and human microbial species but subtype matters

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Lc. lactis MAGs
(dairy)

b

Lc. lactis MAGs
(human + plant-based
fermented food)

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Functional intersections
are higher with plant-
based strains
> Gut microbiome functional enrichment by fermented food is personalized

Modular coalescence between gut and food species

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"Engraftment" as function of existing niche and metabolic pathway
> Fermented food strains are active in gut microbiome

FMP product

* *Streptococcus salivarius subsp. thermophilus strains (CNCM I-2773, CNCM I-2130, CNCM I-2272)*

* *Lactobacillus delbrueckii subsp. bulgaricus (CNCM I-1519)*

* *Bifidobacterium animalis subsp. lactis (CNCM I-2494)*

* *Lactococcus lactis subsp. lactis (CNCM I-1631)*

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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
> Fermented food consumption was associated with gut microbiota metabolic changes

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Flatulogenic diet might increase cell motility and cell growth whereas FMP consumption exhibited the opposite effect

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After FMP intake (TP5), higher responder group showed higher methanogenesis activity than low-responders
> Endgame : From gut microbiome states to next-gen fermented food

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INRAE

Next-Gen Fermented Food: Harnessing Gut Microbiome - LAB symposium

29.08.23 / Julien Tap / fme.micalis.fr

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Trends in Microbiology

Prevent gut microbiome critical transition to strengthen its resilience using next-gen fermented food
> 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
> 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*
> How to design next-gen and sustainable fermented food?

<figure><img src="image_59.png" /></figure>

**Can we demonstrate that fermented food consumption**
**improve human health and restore (maintain) human microbiome symbiotic relationship?**

**What would be the impact**
of transition from **animal-** to **plant-based** fermented food
(anti-nutritional factors, low availability of certain nutrients...) ?

Stéphane Chaillou (Coord.)

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> Take home messages

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

* Fermented foods and biotics can help but **effects may be personalized** thank to gut **microbiota states at baseline**

* Prototyping process of next gen fermented food 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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