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Lactobacillus coryniformis MXJ32 administration ameliorates azoxymethane/dextran sulfate sodium-induced colitis-associated colorectal cancer via resha** intestinal microenvironment and alleviating inflammatory response

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Abstract

Purpose

Gut microbiota has been reported to contribute to either prevent or promote colorectal cancer (CRC), and treatment with probiotics might be a promising intervention method. The present study aimed to evaluate the potential anti-CRC effects of Lactobacillus coryniformis MXJ32 on a colitis-associated (CA)-CRC mouse model.

Methods

The CA-CRC mouse model was induced by a single intraperitoneal injection of 10 mg/kg azoxymethane and followed by three 7-day cycles of 2% dextran sulfate sodium in drinking water with a 14-day recovery period. Mice were supplemented with L. coryniformis MXJ32 by oral gavage (1 × 109 CFU/day/mouse). The CA-CRC attenuating effects of this probiotic were assessed via intestinal barrier integrity, inflammation, and gut microenvironment.

Results

Treatment with L. coryniformis MXJ32 could significantly inhibit the total number of tumors and the average tumor diameter. This probiotic administration prevented the damage of intestinal barrier function by enhancing the expression of tight junction proteins (Occludin, Claudin-1, and ZO-1) and recovering the loss of goblet cells. Moreover, L. coryniformis MXJ32 alleviated intestinal inflammation via down-regulating the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-γ, and IL-17a) and chemokines (Cxcl1, Cxcl2, Cxcl3, Cxcl5, and Ccl7). In addition, L. coryniformis MXJ32 supplementation increased the abundance of some beneficial bacteria (such as SCFAs-producing bacteria, Lactobacillus, Bifidobacterium, Akkermansia, and Faecalibaculum) and decreased the abundance of some harmful bacteria (such as pro-inflammatory bacteria, Desulfovibrio and Helicobacter), which in turn attenuated the overexpression of inflammation.

Conclusion

Lactobacillus coryniformis MXJ32 could effectively ameliorate CA-CRC via regulating intestinal microenvironment, alleviating inflammation, and intestinal barrier damage, which further suggested that L. coryniformis MXJ32 could be considered as a functional food ingredient for the alleviation of CA-CRC.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ANOVA:

Analysis of variance

AOM:

Azoxymethane

CA-CRC:

Colitis-associated colorectal cancer

CFU:

Colony forming unit

CXCR:

C-X-C motif receptor

DAI:

Disease activity index

DSS:

Dextran sulfate sodium

FITC:

Fluorescein isothiocyanate

H&E:

Hematoxylin and eosin

IL:

Interleukin

LDA:

Linear discriminant analysis

LEfSe:

Linear discriminant analysis effect size

LPS:

Lipopolysaccharides

MUC:

Mucin

OUT:

Operational taxonomic unit

PCoA:

Principal coordinates analysis

SCFA:

Short-chain fatty acid

TFF:

Trefoil factor

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labeling

UPGMA:

Unweighted pair group method with arithmetic mean

ZO-1:

Tight junction protein-1

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Acknowledgements

The author thanks the financial support of Post-doctoral Start-up funding (2018) of Northwest A&F University (Z109021804) and National Natural Science Foundation of China (Grant no. 31972043 and 32001652).

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TW, BL, XW, and XL designed the study and wrote the manuscript; TW and LZ performed the experiments; PW and YL analyzed the data; TW, GW, and YS interpreted the results of experiments; YY and YZ prepared figures. All authors read and approved the final manuscript.

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Correspondence to Bianfang Liu, **n Wang or **n Lü.

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The authors have no conflicts of interest.

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All animal experiments were conducted according to the Guide for the Care and Use of Laboratory Animals: Eighth Edition, ISBN-10: 0-309-15396-4, and were approved by the Animal Ethics Committee of **’an Jiaotong University (Permission No. SCXK 2018-001).

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Wang, T., Zhang, L., Wang, P. et al. Lactobacillus coryniformis MXJ32 administration ameliorates azoxymethane/dextran sulfate sodium-induced colitis-associated colorectal cancer via resha** intestinal microenvironment and alleviating inflammatory response. Eur J Nutr 61, 85–99 (2022). https://doi.org/10.1007/s00394-021-02627-8

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