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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Randomized study of Lacticaseibacillus fermented milk in Indonesian elderly houses: Impact on gut microbiota and gut environment
I Nengah Sujaya, Mariyatun Mariyatun, Pratama Nur Hasan, Nancy Eka Putri Manurung, Putrika Citta Pramesi, Mohammad Juffrie, Tyas Utami, Muhammad Nur Cahyanto, Shuta Yamamoto, Takuya Takahashi, Takashi Asahara, Takuya Akiyama, Endang Sutriswati Rahayu
I Nengah Sujaya, School of Public Health, Faculty of Medicine, Udayana University, Denpasar 80230, Bali, Indonesia
Mariyatun Mariyatun, Pratama Nur Hasan, Nancy Eka Putri Manurung, Putrika Citta Pramesi, Endang Sutriswati Rahayu, Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
Mariyatun Mariyatun, Pratama Nur Hasan, Nancy Eka Putri Manurung, Putrika Citta Pramesi, Tyas Utami, Endang Sutriswati Rahayu, Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
Putrika Citta Pramesi, Tyas Utami, Muhammad Nur Cahyanto, Endang Sutriswati Rahayu, Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
Mohammad Juffrie, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
Shuta Yamamoto, Takashi Asahara, Takuya Akiyama, Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi 186-8650, Tōkyō, Japan
Takuya Takahashi, Yakult Honsha European Research Center for Microbiology VOF, Ghent 9052, East Flanders, Belgium
Author contributions: Sujaya IN, Mariyatun M, Hasan PN, Manurung NEP, Pramesi PC, Yamamoto S, Takahashi T, and Asahara T contributed to the investigation of this manuscript; Sujaya IN, Cahyanto MN, and Rahayu ES were involved in the supervision of this manuscript; Sujaya IN and Rahayu ES contributed to the validation of this manuscript; Sujaya IN wrote the original draft; Mariyatun M, Hasan PN, and Akiyama T performed formal analysis; Mariyatun M and Akiyama T contributed to the data curation; Mariyatun M and Hasan PN participated in the resources; Mariyatun M, Juffrie M, Utami T, Yamamoto S, Takahashi T, Asahara T, Akiyama T, and Rahayu ES contributed to the methodology of this manuscript; Mariyatun M performed project administration and funding acquisition; Mariyatun M, Pramesi PC, and Akiyama T were involved in the writing - review and editing of this manuscript; Manurung NEP contributed to the data curated; Juffrie M, Utami T, Cahyanto MN, and Rahayu ES responsible in the conceptualization of this manuscript; Akiyama T contributed to the software.
Supported by the Yakult Honsha Co., Ltd., No. 1226/FTP-UGM/HK/2018.
Institutional review board statement: This study was approved by the Medical and Health Research Ethics Committee, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, with reference number KE/FK/0202/EC/2018 (approval date: March 16, 2018) and an amendment with reference number KE/FK/0202/EC/2018 (approval date: September 13, 2018).
Clinical trial registration statement: This study was registered at ClinicalTrials.gov. The registration number is NCT05308745.
Informed consent statement: All study participants or their legal guardians provided written informed consent before study enrollment.
Conflict-of-interest statement: Yamamoto S, Takahashi T, Asahara T, and Akiyama T are affiliated with Yakult Honsha Co., Ltd. The authors declare that the research was conducted in the absence of commercial or financial relationships that could be construed as potential conflicts of interest.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Data sharing statement: The next-generation sequencing data from this study are publicly available through the DDBJ Sequence Read Archive under accession number DRA014200.
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: Endang Sutriswati Rahayu, PhD, Professor, Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Jl. Flora No. 1 Bulaksumur, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia.
endangsrahayu@ugm.ac.id
Received: December 10, 2024
Revised: January 21, 2025
Accepted: February 24, 2025
Published online: March 28, 2025
Processing time: 107 Days and 4.2 Hours
BACKGROUND
Health maintenance in elderly houses includes management of the gut microbiota and the environment. Lacticaseibacillus paracasei Shirota (LcS) is a probiotic strain that positively affects the human gut. However, the evidence of its effects on the Indonesian population remains limited.
AIM
To investigate the effect of LcS-fermented milk on the gut microbiota and environment of Indonesian elderly houses.
METHODS
This double-blind, randomized, placebo-controlled trial involved 112 participants from Indonesian elderly houses, spanning a 2-week baseline and 24-week treatment. Participants were randomly assigned to probiotic or placebo groups, consuming fermented milk with or without LcS (> 6.5 × 109 colony-forming units). Fecal samples were collected every three months. Gut microbiota analysis was performed using 16S rRNA gene sequencing and reverse transcription quantitative polymerase chain reaction, while gut environment was assessed by measuring fecal organic acids, amino acid metabolites, and stool frequency.
RESULTS
Analyses of 16S rRNA gene sequence data at the 3-month period revealed increased Bifidobacterium and Succinivibrio and decreased Rikenellaceae RC9 gut group in the probiotic group. These shifts were associated with significant differences in β-diversity metrics. The change in Bifidobacterium was confirmed by reverse transcription quantitative polymerase chain reaction, demonstrating higher abundance in the probiotic group than in the placebo group (8.5 ± 1.1 vs 8.0 ± 1.1, log10 bacterial cells/g; P = 0.044). At 6-month period, the differences in Succinivibrio and Rikenellaceae RC9 gut group persisted. The probiotic group showed higher butyrate levels than the placebo group at the 6-month period (5.04 ± 3.11 vs 3.95 ± 2.89, μmol/g; P = 0.048). The effect on amino acid metabolites and stool frequency was not significant.
CONCLUSION
Daily intake of LcS positively affects the gut microbiota and environment of people living in Indonesian elderly houses.
Core Tip: The daily consumption of fermented milk containing Lacticaseibacillus paracasei Shirota significantly altered the gut microbiota among individuals in Indonesian elderly houses. Notably, these changes included increases in Bifidobacterium and Succinivibrio and a decrease in the Rikenellaceae RC9 gut group. These modifications are associated with an improvement in the gut environment, as indicated by elevated butyrate levels.
