(OR07-01-26) Resistant Starch Supplementation Modulates Gut Microbiota and Metabolic Outcomes in β- Glucuronidase-Inhibited Estrogen-Deficient Mice

Saturday, July 25, 2026

4:30 PM - 4:42 PM ET

Location: National Harbor 4-5

Emerging Leaders in Nutrition Science Poster Competition

Presenting Author(s)

Femi Olawale, PhD (he/him/his)

Graduate research assistant
Oklahoma State University
stillwater, Oklahoma, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

RC

Ranjitha Chandrashekar

Oklahoma State University
stillwater, Oklahoma, United States
BS

Brooke Sutton

Oklahoma State University
stillwater, Oklahoma, United States
SA

Sanmi Alake

Oklahoma State University
stillwater, Oklahoma, United States
MJ

Megan Justice

Oklahoma State University
stillwater, Oklahoma, United States
HH

Hong Hwang

Oklahoma State University
stillwater, Oklahoma, United States
SJ

Samuel Jeyasingh

Oklahoma State University
stillwater, Oklahoma, United States
JF

Jorja Ford

Oklahoma State University
stillwater, Oklahoma, United States
YA

Yabsira Argeta

Oklahoma State University
stillwater, Oklahoma, United States
AS

Anthony Schilmiller

Michigan State University, Michigan, United States
WC

Winyoo Chowanadisai

Oklahoma State University
stillwater, Oklahoma, United States
BS

Brenda Smith

Indiana University, Indiana, United States
EL

Edralin Lucas

Oklahoma State University, Oklahoma, United States

Disclosure(s):

Femi Olawale, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Gut microbial β-glucuronidase (gmGUS) regulates estrogen metabolism and is relevant in menopause, which is associated with gut dysbiosis and metabolic dysfunction. This study evaluated the effects of retrograded resistant starch (RS3) on gut microbiota composition and metabolic outcomes in gmGUS-inhibited estrogen-deficient mice.

Methods: Forty-eight 3-month-old female C57BL/6 mice were all rendered estrogen-deficient by daily VCD injections (160 mg/kg) for 30 d and then randomized to control (CON, AIN-93M) or 5% (wt/wt) RS3 diets with or without gmGUS inhibition for 14 weeks. Body composition (DXA), cecal microbiota (16S rRNA sequencing), fecal gmGUS activity (enzymatic assay), and short-chain fatty acids (GC-FID) were assessed. Metabolic outcomes, including fasting glucose (FBG), glucose tolerance, and serum lipids, were also measured. Data were analyzed by 2-way ANOVA with diet and gmGUS inhibition as factors, followed by Tukey’s post hoc test when P < 0.05.

Results: The effect of the gmGUS inhibitor was confirmed by decreased gmGUS activity. A main effect of diet (P_diet = 0.003) was also observed with RS3 increasing gmGUS activity vs. CON. Also, gmGUS inhibition significantly shifted gut microbial composition, reducing Bifidobacterium (a key estrobolome-associated SCFA-producing taxon) and increasing Clostridium genera; whereas, RS3 attenuated Clostridium and increased Bifidobacterium. RS3 supplementation significantly increased acetate (P_diet < 0.001), propionate (P_diet = 0.017), and n-butyrate (P_diet = 0.006). RS3 also altered body composition by reducing % fat mass (P_diet = 0.012) and increasing % lean mass (P_diet = 0.015) compared to CON. Significant interaction effects were observed for FBG (P_{inh x diet} = 0.001) and glucose tolerance (P_{inh x diet} = 0.002), with RS3 modulating both indicators of glucose homeostasis induced by gmGUS inhibition. RS3 diet also lowered serum total cholesterol (P_diet = 0.013) and LDL (P_diet = 0.009) concentrations.

Conclusions: Inhibition of gmGUS in estrogen-deficient mice disrupted gut microbiota and glucose homeostasis. RS3 increased Bifidobacterium, improved glucose regulation, reduced adiposity, and lowered circulating lipids, suggesting mitigation of metabolic dysfunction via gut–host signaling.

Funding Sources: NIH-NIA/NICCH and Jim and Lynne Williams Professorship