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Effect of Lactobacillus Rhamnosus GG for Regulation of Inflammatory Response in Radiation-Induced Enteritis

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Abstract

The purpose of this study was to investigate the role of Lactobacillus rhamnosus GG (LGG) probiotics in radiation enteritis using in vivo mice. A total of 40 mice were randomly assigned to four groups: control, probiotics, radiotherapy (RT), and RT + probiotics. For the group of probiotics, 0.2 mL of solution that contained 1.0 × 108 colony-forming units (CFU) of LGG was used and orally administered daily until sacrifice. For RT, a single dose of 14 Gy was administered using a 6 mega-voltage photon beam to the abdominopelvic area. Mice were sacrifice at day 4 (S1) and day 7 (S2) after RT. Their jejunum, colon, and stool were collected. A multiplex cytokine assay and 16 s ribosomal RNA amplicon sequencing were then performed. Regarding cytokine concentrations in tissues, pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 and monocyte chemotactic protein-1, showed significantly decreased protein levels in colon tissues of the RT + probiotics group than in the RT alone group (all p < 0.05). As for comparing microbial abundance through alpha-diversity and beta-diversity, no significant differences were observed between the RT + probiotics and RT alone groups, except for an increase in alpha-diversity in the stool of the RT + probiotics group. Upon analysis of differential microbes based on treatment, the dominance of anti-inflammatory-related microbes, such as Porphyromonadaceae, Bacteroides acidifaciens, and Ruminococcus, was observed in the jejunum, colon, and stool of the RT + probiotics group. With regard to predicted metabolic pathway abundances, the pathways associated with anti-inflammatory processes, such as biosynthesis of pyrimidine nucleotides, peptidoglycans, tryptophan, adenosylcobalamin, and propionate, were differentially identified in the RT + probiotics group compared to the RT alone group. Protective effects of probiotics on radiation enteritis were potentially derived from dominant anti-inflammation-related microbes and metabolites.

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Data Availability

The data that support the findings of this study are openly available in figshare at https://doi.org/10.6084/m9.figshare.21101686, and within the article and its supplementary materials. The 16s ribosomal RNA raw sequencing data can be found at the BioProject database (ID: PRJNA934953).

Abbreviations

RT:

Radiotherapy

CFU:

Colony-forming units

LGG:

Lactobacillus rhamnosus GG

TNF-α:

Tumor Necrosis Factor-α

IL-6:

Interleukin-6

MCP-1:

Monocyte Chemotactic Protein-1

IL-12p40:

Interleukin-12p40

IL-1α:

Interleukin-1α

IL-1β:

Interleukin-1β

IL-10:

Interleukin-10

MPO:

Myeloperoxidase

NMDS:

Non-metric multidimensional scaling

LDA:

Linear discriminant analysis

ANOVA:

One-way analysis of variance

FDR:

False Discovery Rate

SCFA:

Short-chain fatty acids

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Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant Number: 2019R1A2C1002071), the New Faculty Startup Fund, 3020200090 from SNUH Research Fund, and funded by the Seoul Metropolitan Government-Seoul National University Boramae Medical Center (Grant Number 03-2017-19).

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Author notes

  1. Sung Uk Lee and Bum-Sup Jang made equal contributions to this study.

Authors and Affiliations

  1. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, South Korea

    Sung Uk Lee, Bum-Sup Jang, Ji Hyun Chang & Hak Jae Kim

  2. Proton Therapy Center, National Cancer Center, Goyang, South Korea

    Sung Uk Lee

  3. Department of Radiation Oncology, Seoul National University Hospital, Seoul, South Korea

    Bum-Sup Jang, Sun Hwa Lee, Ji Hyun Chang & Hak Jae Kim

  4. Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, South Korea

    Yi Rang Na & Sunwoo Han

  5. Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Hak Jae Kim

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Contributions

SL and BJ were involved in the conception design, analysis and interpretation of the data, and drafting of the manuscript. YN and SL collected and analyzed the data and assisted in manuscript drafting. SH collected and analyzed the data. JC and HK developed the conception design, analyzed and interpreted the data, and revised the manuscript critically for intellectual content.

Corresponding authors

Correspondence to Ji Hyun Chang or Hak Jae Kim.

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The Institutional animal care and use committee of Seoul National University Hospital approved the experimental protocol (IACUC NO. 18–0096).

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Lee, S.U., Jang, BS., Na, Y.R. et al. Effect of Lactobacillus Rhamnosus GG for Regulation of Inflammatory Response in Radiation-Induced Enteritis. Probiotics & Antimicro. Prot. 16, 636–648 (2024). https://doi.org/10.1007/s12602-023-10071-9

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