(1143) Impact of the gut microbiome on responsiveness to iron supplementation in a prospective, interventional trial

Friday, February 10, 2023

3:30 PM – 5:00 PM

Objective: Gut iron absorption is regulated to allow for optimal bioavailability & overcome iron losses during menstruation. However, clinical response to iron supplementation is unpredictable. We hypothesized that the gut microbiome may explain iron absorption disparity among healthy, non-anemic menstruating people (pwm).

Study Design: Pwm (n=26) without a known history of anemia or iron deficiency were included in our open label, prospective, interventional trial. Participants received 14 days of 65mg elemental iron, then were followed for a 21-day wash-out period (35 days total). Stool (8 samples) & blood (3 samples- baseline, d14 & d35) were collected for microbiome analyses as well as iron & anemia indices. DNA extractions from stool samples underwent 16S amplicon sequencing & bioinformatic analysis of microbial ASVs (DADA2). Ecological diversity metrics, taxonomic comparisons, & unsupervised clustering with Dirichlet multinomial mixtures (DMM) were performed.

Results: Participants were naively classified by percentiles of ferritin response (Δ ferritin): fast (n=6, Δ ≥75^th), slow (n=7, median< Δ < 75^th), & non-responders (n=13, < median). Within-subject taxonomical diversity naively clustered into 3 distinct gut microbiome ecologies which significantly correlated with ferritin responder class (α diversity, Fig. 1 A,B). Between group diversity was significantly different among iron responders (β diversity weighted UniFrac, p=0.041; posthoc tukey p< 0.0001). Ferritin response was associated with a microbiome ecology comprised of a greater number of rare taxa (Fig. 1 C-E). Multivariate linear modeling identified 7 genera in the gut microbiome which drove ferritin response (Fig. 2).

Conclusion: The microbiome gut ecology independently classifies iron supplementation responders & non-responders. Consistent with the principles of xenobiotics, microbes may enable differential iron absorption. Modulating the gut microbiome offers a novel means of improving iron supplementation efficacy during reproduction.

Primary & Presenting Author(s)

Sarah E. Detlefs, MD, MS
Assistant Professor
Baylor College of Medicine
Houston, Texas, United States

Coauthor(s)

Michael D. Jochum, Jr., PhD
Postdoctoral Research Associate
Baylor College of Medicine
Houston, Texas, United States
Maryshe S. Zietsman, BSA
Medical Student
Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children’s Hospital
Houston, Texas, United States
Maxim D. Seferovic, PhD
Assistant Professor
Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children’s Hospital
Houston, Texas, United States
Erin Bolte, MSc (she/her/hers)
MD/PhD Student
Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine
Houston, Texas, United States
SD
Sridevi Devaraj, DABBC, PhD
Professor of Pathology& Immunology
Baylor College of Medicine
Houston, Texas, United States
Kjersti M. Aagaard, MD,PhD
Professor and Vice Chair of Research Department of Obstetrics and Gynecology, Division of MFM
Texas Children's and Baylor College of Medicine
Houston, Texas, United States