Feeding Microbes: Nutrition, Microbiome, Metabolism, and Health (Oral Session 6)

(OR06-01-25) Combined Prebiotic Dietary Inulin and VSL#3 Probiotics Modulate Gut Metabolites to Improve Energy Balance and Glucose Metabolism in Diet-Induced Obese Mice

Sunday, June 1, 2025

10:00 AM – 10:12 AM ET

Location: S230 CD

Emerging Leaders in Nutrition Science Poster Competition

Presenting Author(s)

Karolline S. May, PhD (she/her/hers)

Postdoctoral Scholar
University of Washington
Seattle, Washington, United States

Disclosure(s): OrsoBio: Consultant (Ongoing)

Co-Author(s)

AL

Angel A. Lee

University of Washington
Seattle, Washington, United States
SW

Shari Wang

University of Washington
Seattle, Washington, United States
RA

Robin Altman

University of Washington
Seattle, Washington, United States
MZ

Meifan Zhang

Rutgers University
New Jersey, New Jersey, United States
CB

Caeley L. Bryan

University of Washington
Seattle, Washington, United States
BL

Brian T. Layden, M.D., Ph.D.

Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA
Chicago, Illinois, United States
MB

Martin J. Blaser

Rutgers University
Piscataway, New Jersey, United States
GM

Gregory J. Morton

University of Washington
Seattle, Washington, United States
Ld

Laura J. den Hartigh

University of Washington
Seattle, Washington, United States

Objectives: Inulin, a prebiotic dietary fiber, reduces body weight gain and improves glucose metabolism in obese mice. In the current study, we sought to determine whether combining inulin supplementation with VSL#3, a probiotic blend, could further improve energy balance and glucose metabolism by increasing microbial short-chain fatty acids (SCFA), which activate free fatty acid receptor 2 (FFAR2) in adipose tissue.

Methods: Eight-week-old male C57BL/6J wild-type (WT) and adipocyte FFAR2-knockout (Ad-FFAR2 KO) mice were fed a high-fat high-sucrose (HFHS) diet for 8 weeks. Mice were then randomized into experimental groups to receive either continued HFHS (n=6-13), or HFHS containing inulin (10% w/w chicory root inulin; n=5-12), with and without VSL#3 (7x10⁸ CFU, given 3 times/week via oral gavage; n=7-15), for an additional 5 weeks. Body weight was recorded weekly. Body composition and intraperitoneal glucose and insulin tolerance tests were performed. Blood and feces were collected for SCFA and insulin quantification. White adipose tissue from epididymal (EWAT), inguinal (IWAT), and mesenteric (MWAT) depots, and small intestine were harvested at study termination.

Results: Ad-FFAR2 KO mice exhibited higher body weight and increased body fat compared to WT mice fed a HFHS diet. While inulin blunted body weight and fat gain in WT mice, it did not have the same effect in Ad-FFAR2 KO mice. In WT mice, these adiposity changes were accompanied by reduced serum amyloid A3 (Saa3) and increased adiponectin mRNA in EWAT. However, the combined inulin and VSL#3 did not alter body weight, fat composition, or glucose and insulin tolerance in either genotype, but did lower fasting glucose levels. These effects of VSL#3 in both genotypes were accompanied by higher levels of fecal and plasma SCFA, including acetate, propionate, and butyrate.

Conclusions: Our data suggest that combined dietary inulin and VSL#3 supplementation improve energy balance, glucose metabolism, and inflammation in diet-induced obese mice via modulating the responsiveness of adipocytes to gut SCFA via FFAR2. These findings highlight the potential of this combined intervention as a potential strategy for managing obesity-related outcomes.

Funding Sources: American Heart Association; Nutrition Obesity Research Center Pilot & Feasibility; USDA NIFA