Bile acid dysmetabolism in Bangladeshi infants associated with poor linear growth, enteric inflammation, and small intestine bacterial overgrowth

doi:10.3748/wjg.v31.i43.111609

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Nov 21, 2025; 31(43): 111609
Published online Nov 21, 2025. doi: 10.3748/wjg.v31.i43.111609

Bile acid dysmetabolism in Bangladeshi infants associated with poor linear growth, enteric inflammation, and small intestine bacterial overgrowth

Farah Hasan, Phillip B Hylemon, Rashidul Haque, William A Petri, Abu Syed Golam Faruque, Beth D Kirkpatrick, Madud Alam, Tahsin Ferdous, Talat Shama, Brett Moreau, Girija Ramakrishnan, Huiping Zhou, Alden Chesney, Felix Medrano Garcia, Ekaterina Smirnova, Preethi Prem, Yingsi Huang, Rashmi Bojja, Anubhav Thapaliya, Jeffrey R Donowitz

Farah Hasan, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, United States

Phillip B Hylemon, Huiping Zhou, Department of Microbiology and Immunology and Stravitz-Sanyal Institute for Liver Disease & Metabolic Health, Virginia Commonwealth University, Richmond, VA 23298, United States

Rashidul Haque, Madud Alam, Tahsin Ferdous, Talat Shama, Infectious Diseases Division, ICDDR,B, Dhaka 1212, Bangladesh

William A Petri, Brett Moreau, Girija Ramakrishnan, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA 22908, United States

Abu Syed Golam Faruque, Centre for Nutrition & Food Security, International Centre for Diarrhoeal Disease Research, ICDDR,B, Dhaka 1212, Bangladesh

Beth D Kirkpatrick, Madud Alam, Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, VT 05405, United States

Huiping Zhou, Felix Medrano Garcia, Richmond Veterans Medical Center, Richmond Veterans Medical Center, Richmond, VA 23249, United States

Alden Chesney, Division of Clinical Pathology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, United States

Ekaterina Smirnova, Preethi Prem, Department of Biostatistics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, United States

Preethi Prem, College of Medicine, Carle Illinois College of Medicine, Champaign, IL 61801, United States

Yingsi Huang, Department of Management Science, Miami Herbert Business School, Coral Gables, FL 33146, United States

Rashmi Bojja, College of Osteopathic Medicine, Edward Via College of Osteopathic Medicine, Blacksburg, VA 24060, United States

Anubhav Thapaliya, Medical School, The University of Texas Southwestern Medical Center, Dallas, TX 75390, United States

Jeffrey R Donowitz, Division of Pediatric Infectious Diseases, University of Virginia, Charlottesville, VA 22903, United States

Co-corresponding authors: Farah Hasan and Jeffrey R Donowitz.

Author contributions: Hasan F was involved in conception of the study, study design, statistical analysis, interpretation of results, and primary authorship of the manuscript; Hylemon PB was involved in conception of the study, study design, interpretation of results, and authorship of the manuscript; Haque R was involved in conception of the study, study design, sample collection, interpretation of results, and authorship of the manuscript; Petri WA was involved in conception of the study, interpretation of results, and authorship of the manuscript; Faruque ASG and Kirkpatrick BD were involved in conception of the study, sample collection, and authorship of the manuscript; Alam M was involved in sample collection, interpretation of results, and authorship of the manuscript; Ferdous T and Shama T were involved in sample collection and authorship of the manuscript; Moreau B, Ramakrishnan G, and Zhou H were involved in sample analysis, interpretation of results, and authorship of the manuscript; Chesney A and Medrano Garcia F were involved in study design, sample collection and authorship of the manuscript; Smirnova E, Prem P, Huang Y, Bojja R, and Thapaliya A were involved in statistical analysis, interpretation of results, and authorship of the manuscript; Donowitz JR was involved in conception of the study, study design, statistical analysis, interpretation of results, and authorship of the manuscript. Hasan F and Donowitz JR contributed equally as co-corresponding authors.

Supported by Children’s Hospital Foundation at VCU, No. 1K23HD097282 (to Donowitz JR); National Institutes of Health, No. 5R01AI043596 (to Donowitz JR); Bill and Melinda Gates Foundation, No. OPP1017093; VA Merit Award, No. 1I01BX005730; VA ShEEP Grants, No. 1 IS1 BX004777-01; National Institutes of Health Grant, No. 2R56DK115377-05A1; PIDS Summer Research Scholars Award; VCU SOM Dean’s Summer Research Fellowship; and Research Career Scientist Award from the Department of Veterans Affairs, No. IK6BX004477.

Institutional review board statement: The collection and analysis of Bangladeshi samples was approved by the Ethics and Research Review Committees at the ICDDR,B and the Institutional Review Board at the University of Virginia. Reliance agreements between the University of Virginia and the ICDDR,B with Virginia Commonwealth University were also established for this study. For the American control group, the study was approved by the Institutional Review Board at Virginia Commonwealth University.

Informed consent statement: Informed consent for participation was received by both parents of enrolled children. A waiver of consent was obtained to use discarded samples.

Conflict-of-interest statement: There are no conflicts of interest.

Data sharing statement: Original data, figures and statistical data are available upon reasonable requests from the corresponding author at fhasan999@gmail.com.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Farah Hasan, MD, Virginia Commonwealth University, School of Medicine, 1201 E Marshall St, Richmond, VA 23298, United States. hasanf2@vcu.edu

Received: July 8, 2025
Revised: August 18, 2025
Accepted: October 27, 2025
Published online: November 21, 2025
Processing time: 135 Days and 17.1 Hours

Abstract

BACKGROUND

Environmental enteric dysfunction (EED) is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis. Bile acids serve to facilitate lipid digestion and absorption, regulate metabolic pathways associated with childhood growth and inflammation, and may be affected by EED.

AIM

To investigate bile acid metabolism in Bangladeshi children with EED and its association with growth impairment.

METHODS

We conducted a cross-sectional study of 100 Bangladeshi infants (aged 6-9 months) and quantified serum and fecal bile acids using LC-MS/MS. We compared profiles to a control group of 6 American children (6-12 months) and 80 older Bangladeshi children (aged 2 years).

RESULTS

Bangladeshi infants had higher levels of plasma unconjugated primary (65.23% vs 44.25%, P = 0.003) and sulfated primary bile acids (12.98% vs < 0.001%, P = 0.01), with lower primary conjugated bile acids (0.69% vs 2.74%, P ≤ 0.001) compared to American children. Stool unconjugated primary bile acids were inversely associated with weight-for-age [regression coefficient (β) = -0.01, P = 0.01] and height-for-age Z scores (β = -0.01, P = 0.03). Conjugated secondary bile acids were inversely associated with small intestine bacterial overgrowth (β = -1096.68, P = 0.05). Fecal myeloperoxidase was associated with sulfated secondary bile acids (β = -0.40, P = 0.04). Compared to 2-year-old children, the Bangladeshi infant’s serum had higher levels of unconjugated primary bile acids (65.23% vs 9.20%, P ≤ 0.001) and lower levels of primary conjugated bile acids (0.69% vs 80.38%, P ≤ 0.001).

CONCLUSION

Our data suggests an age-dependent defect in conjugation of primary bile acids in Bangladeshi children with compensatory hydrophilic shunting. Additionally, bile acid profiles are associated with intestinal overgrowth.

Keywords: Bile acid metabolism; Malnutrition; Environmental enteric dysfunction; Small intestinal bacterial overgrowth; Bangladesh

Core Tip: This study identifies a previously unrecognized defect in bile acid conjugation among Bangladeshi infants with environmental enteric dysfunction, linking altered bile acid metabolism to poor growth and intestinal inflammation. Elevated unconjugated primary bile acids were strongly associated with anthropometry. Further, the findings highlight a possible age-related delay in maturation of bile acid conjugation pathways in impoverished children. This study may provide the initial insights for exploring novel therapeutic targets through bile acid pathways for treating malnourished children worldwide.