# Modulation de l'inflammation liée à l'obésité en utilisant des extraits de prébiotiques fermentés par des bactéries intestinales : développement et caractérisation in vitro

Arthur Chervet, Rawan Nehme, Clémence Defois-Fraysse, Caroline Decombat, Bertrand Evrard, Edith Filaire, Jean-Yves Berthon, Assia Dreux-Zigha, Laetitia Delort, Florence Caldefie-Chezet

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Arthur Chervet, Rawan Nehme, Clémence Defois-Fraysse, Caroline Decombat, Bertrand Evrard, et al. Modulation de l'inflammation liée à l'obésité en utilisant des extraits de prébiotiques fermentés par des bactéries intestinales : développement et caractérisation in vitro. 3ème journée scientifique pour le CIR3 - CAP2025, Oct 2024, Clermont-ferrand, France. [hal-04875936](https://hal.science/hal-04875936v1)

HAL Id: hal-04875936

https://hal.science/hal-04875936v1

Submitted on 13 Jan 2025

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Distributed under a Creative Commons Attribution 4.0 International License
# Modulation of obesity-related inflammation using prebiotic extracts fermented by intestinal bacteria: development and *in vitro* characterization

A. Chervet¹, R. Nehme¹, C. Defois-Fraysse², C. Decombat¹, B. Evrard¹, E. Filaire¹, J.-Y. Berthon³, A. Dreux-Zigha², L. Delort¹, A. F. Caldefie-Chezet¹
¹Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, Clermont-Ferrand, France, ²Greencell, Saint-Beauzire, France, ³Greentech SA, Saint-Beauzire, France

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Phytoprob'inoV

Labcom

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GREENTECH

BIOTECHNOLOGIES

ECREIN

Micro-environnement CelluleRE. Immunomodulation et Nutrition

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UNH

Unité de Nutrition Humaine

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UNIVERSITÉ
Clermont
Auvergne

INRAO

anr®

aRT

ASSOCIATION NATIONALE
RECHERCHE TECHNOLOGIE

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L'EUROPE S'ENGAGE
en region
Auvergne-Rhône-Alpes
avec le FEDER

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I-SITE
CLERMONT
Clermont Auvergne Project

## Background

Obesity, which has become a global public health issue, is defined by an excessive accumulation of body fat. It is a chronic disease and a major risk factor for many other pathologies development. Obesity epidemiology demonstrates that its prevalence has gradually increased over the last few decades. According to WHO, more than 890 million persons are estimated to be obese in 2022.

<figure><img src="image_8.png" /></figure>

## Objective

The aim of the project is to develop new natural health products for nutraceuticals and dermo-cosmetics. The extracts are obtained from the fermentation of a prebiotic and a probiotic. 37 combinations have been developed and investigated. Two of them have been retained for additional studies, including Phyto-Probiotics 21 (PP21)

<figure><img src="image_9.png" /><figcaption>PP21 (Phyto-Probiotic production)</figcaption></figure>

## Targets

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Obesity

<figure><img src="image_11.png" /></figure>

<figure><img src="image_12.png" /></figure>

Low-grade inflammation

## Methods & Results

<figure><img src="image_13.png" /><figcaption>THP-1 polarization into M0-like or M1-like macrophages</figcaption></figure>

<figure><img src="image_14.png" /><figcaption>PBMCs pro-inflammatory cytokine secretion</figcaption></figure>

<figure><img src="image_15.png" /></figure>

<figure><img src="image_16.png" /><figcaption>PP21 lowered the secretion of IL-17A & IFNy</figcaption></figure>

Leptin : pro-inflammatory adipokine
Adiponectin : anti-inflammatory adipokine
HSL : Enzyme that converts triglycerides in adipose tissue into fatty acids

<caption>PP21 reduced the gene expression of M1-like markers (TNF-α, IL-6) and enhanced IL-10 expression (M2 marker)</caption>

<figure><img src="image_17.png" /><figcaption>Co-culture between mature obese adipospheroids / M1-like</figcaption></figure>

In order to mimic the reality of the adipose tissue and to copy the existing cell-cell interaction, mature adipospheroids (BMI>31) were co-cultured with M1-like macrophages. The adipospheroids were grown and differentiated for 10 days before being co-cultured M1-like macrophages. On the day of co-culture, the extract was applied for 24 hours.

<figure><img src="image_18.png" /></figure>

<figure><img src="image_19.png" /><figcaption>PP21 lowered the gene expression of M1-like markers (TNF-α, IL-6, IL-8), and leptin</figcaption></figure>

<figure><img src="image_20.png" /><figcaption>and up-regulated adiponectin and HSL expression</figcaption></figure>

<figure><img src="image_21.png" /></figure>

<figure><img src="image_22.png" /><figcaption>PP21 enhanced secretion of adiponectin and decreased for IFNy, but not significantly</figcaption></figure>

<caption>High variability for leptin and IL-6</caption>

## Conclusion

PP21 extract might be a promising option for managing obesity by lowering low-grade inflammation and modulating adipokine production