Probiotic Supplementation With Bifidobacterium longum Subsp. Longum BL21 Improves Glycemic Control and Modulates Gut Microbiota in Type 2 Diabetes - A Randomized Controlled Trial

Sep 30, 2026

Uploaded by Jake

Type 2 diabetes mellitus (T2DM) remains a major global health challenge, with emerging evidence pointing to gut microbiota modulation as a therapeutic avenue. This study assessed efficacy and safety of Bifidobacterium longum subsp. longum BL21 as adjunctive therapy to metformin in T2DM through a 12-week randomized, double-blind, placebo-controlled trial. The primary endpoint was hemoglobin A1c (HbA1c), with secondary outcomes including fasting blood glucose, insulin resistance, lipid profiles, and microbiota composition. BL21 significantly reduced HbA1c (p=0.026), with non-significant trends for FBG and insulin resistance, good tolerability, and beneficial microbiota shifts alongside reduced pathogenic taxa.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

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Introduction

Gut microbiota and T2DM rationale

Probiotics and evidence background

BL21 and study motivation

Food Science & Nutrition ORIGINAL ARTICLE OPEN ACCESS Probiotic Supplementation With Bifidobacterium longum Subsp. Longum BL21 Improves Glycemic Control and Modulates Gut Microbiota in Type 2 Diabetes: A Randomized Controlled Trial Chengsheng Zhu1 | Yinhua Liu1 | Yanyan Chen1 | Zhiying Wang1 | Ya Gao2 | Fei Xu1 | Junyi Huang3 1College of Food Science and Technology, Henan University of Technology, Zhengzhou, China | 2Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China | 3Food Nutrition and Chronic Disease, Intervention Laboratory, School of Life Sciences, Shanghai University, Shanghai, China Correspondence: Fei Xu ([xu.fei@haut.edu.cn](xu.fei@haut.edu.cn)) | Junyi Huang ([jy-huang@shu.edu.cn](jy-huang@shu.edu.cn)) Received: 1 July 2025 | Revised: 12 November 2025 | Accepted: 29 December 2025 Keywords: Bifidobacterium longum subsp. longum | glycemic control | gut microbiota modulation | type 2 diabetes mellitus ABSTRACT Type 2 diabetes mellitus (T2DM) remains a major global health challenge, with emerging evidence highlighting the therapeutic potential of gut microbiota modulation. This study aimed to evaluate the efficacy and safety of Bifidobacterium longum subsp. longum BL21 as an adjunctive therapy to metformin in patients with T2DM. In this 12-week, randomized, double-blind, placebocontrolled trial, patients with T2DM received either metformin plus BL21 or metformin plus placebo. The primary endpoint was the change in hemoglobin A1c (HbA1c), while secondary endpoints included changes in fasting blood glucose (FBG), insulin resistance, lipid profiles, and gut microbiota composition. Supplementation with BL21 led to a significant reduction in HbA1c levels (p = 0.026) compared with placebo. Non-significant trends toward reduction were also observed for FBG and insulin resistance. The intervention was well tolerated, with a safety profile comparable to placebo. Gut microbiota analysis revealed an increase in beneficial genera, including Bifidobacterium and Faecalibacterium, alongside a reduction in pathogenic taxa in the BL21 group. As an adjunct to metformin, BL21 supplementation improved glycemic control and modulated gut microbiota in patients with T2DM. These findings support the potential of BL21 as a novel adjunctive strategy for T2DM management, warranting further validation in larger and longer-term studies. Clinical Trial Registration Number: ChiCTR2300073299. 1 | Introduction Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, β-cell dysfunction, and impaired glucose metabolism (Diane et al. 2022; Liu et al. 2025) . The global prevalence of T2DM has been rising steadily, establishing it as one of the most significant public health challenges worldwide. According to the International Diabetes Federation (IDF), approximately 537 million adults aged 20–79 years were living with diabetes in 2021, with T2DM accounting for over 90% of cases (Fernández-Cao et al. 2024; Abd El-Razik Siam et al. 2023). This number is projected to increase to 783 million by 2045, primarily driven by aging populations, sedentary lifestyles, and rising obesity rates, particularly in low-and middleincome countries (Sun et al. 2022) . Despite the availability of a wide range of pharmacological treatments, including metformin, sulfonylureas, and newer agents such as glucagon-like peptide-1 (GLP-1) receptor agonists, a substantial proportion of This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2026 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC. Food Science & Nutrition, 2026; 14:e71437 1 of 11 [https://doi.org/10.1002/fsn3.71437](https://doi.org/10.1002/fsn3.71437) patients fail to achieve optimal

FAQs

What was the main objective of the trial involving BL21?

To evaluate the efficacy and safety of Bifidobacterium longum subsp. longum BL21 as an adjunct to metformin in patients with type 2 diabetes.

What was the primary endpoint used to judge effectiveness?

The primary endpoint was the change in hemoglobin A1c (HbA1c).

What microbiota changes were observed after BL21 supplementation?

Gut microbiota analysis showed increased beneficial genera such as Bifidobacterium and Faecalibacterium, along with reductions in pathogenic taxa in the BL21 group.

Sep 30, 2026

Uploaded by Jake