TY - JOUR

T1 - Experimental diets dictate the metabolic benefits of probiotics in obesity

AU - Larsen, Ida Søgaard

AU - Choi, Béatrice S.Y.

AU - Föh, Bandik

AU - Kristensen, Nanna Ny

AU - Ouellette, Adia

AU - Haller, Rune Falkenberg

AU - Olsen, Peter Bjarke

AU - Saulnier, Delphine

AU - Sina, Christian

AU - Jensen, Benjamin A.H.

AU - Marette, André

N1 - Publisher Copyright: © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.

PY - 2023

Y1 - 2023

N2 - Growing evidence supports the use of probiotics to prevent or mitigate obesity-related dysmetabolism and non-alcoholic fatty liver disease (NAFLD). However, frequent reports of responders versus non-responders to probiotic treatment warrant a better understanding of key modifiers of host–microbe interactions. The influence of host diet on probiotic efficacy, in particular against metabolic diseases, remains elusive. We fed C57BL6/J mice a low fat reference diet or one of two energy-matched high fat and high sucrose diets for 12 weeks; a classical high fat diet (HFD) and a customized fast food-mimicking diet (FFMD). During the studies, mice fed either obesogenic diet were gavaged daily with one of two probiotic lactic acid bacteria (LAB) strains previously classified as Lactobaccillus, namely Limosilactobacillus reuteri (L. reuteri)or Lacticaseibacillus paracaseisubsp. paracasei (L. paracasei), or vehicle. The tested probiotics exhibited a reproducible efficacy but dichotomous response according to the obesogenic diets used. Indeed, L. paracaseiprevented weight gain, improved insulin sensitivity, and protected against NAFLD development in mice fed HFD, but not FFMD. Conversely, L. reuteri improved glucoregulatory capacity, reduced NAFLD development, and increased distal gut bile acid levels associated with changes in predicted functions of the gut microbiota exclusively in the context of FFMD-feeding. We found that the probiotic efficacy of two LAB strains is highly dependent on experimental obesogenic diets. These findings highlight the need to carefully consider the confounding impact of diet in order to improve both the reproducibility of preclinical probiotic studies and their clinical research translatability.

AB - Growing evidence supports the use of probiotics to prevent or mitigate obesity-related dysmetabolism and non-alcoholic fatty liver disease (NAFLD). However, frequent reports of responders versus non-responders to probiotic treatment warrant a better understanding of key modifiers of host–microbe interactions. The influence of host diet on probiotic efficacy, in particular against metabolic diseases, remains elusive. We fed C57BL6/J mice a low fat reference diet or one of two energy-matched high fat and high sucrose diets for 12 weeks; a classical high fat diet (HFD) and a customized fast food-mimicking diet (FFMD). During the studies, mice fed either obesogenic diet were gavaged daily with one of two probiotic lactic acid bacteria (LAB) strains previously classified as Lactobaccillus, namely Limosilactobacillus reuteri (L. reuteri)or Lacticaseibacillus paracaseisubsp. paracasei (L. paracasei), or vehicle. The tested probiotics exhibited a reproducible efficacy but dichotomous response according to the obesogenic diets used. Indeed, L. paracaseiprevented weight gain, improved insulin sensitivity, and protected against NAFLD development in mice fed HFD, but not FFMD. Conversely, L. reuteri improved glucoregulatory capacity, reduced NAFLD development, and increased distal gut bile acid levels associated with changes in predicted functions of the gut microbiota exclusively in the context of FFMD-feeding. We found that the probiotic efficacy of two LAB strains is highly dependent on experimental obesogenic diets. These findings highlight the need to carefully consider the confounding impact of diet in order to improve both the reproducibility of preclinical probiotic studies and their clinical research translatability.

KW - diet-induced obesity

KW - dietary interaction

KW - insulin resistance

KW - MAFLD

KW - microbiota

KW - NAFLD

KW - NASH

KW - Probiotics

UR - http://www.scopus.com/inward/record.url?scp=85150840610&partnerID=8YFLogxK

U2 - 10.1080/19490976.2023.2192547

DO - 10.1080/19490976.2023.2192547

M3 - Journal article

C2 - 36945120

AN - SCOPUS:85150840610

VL - 15

JO - Gut Microbes

JF - Gut Microbes

SN - 1949-0976

IS - 1

M1 - 2192547

ER -