Skip to main content
Top
Published in: Chinese Medicine 1/2022

Open Access 01-12-2022 | Respiratory Microbiota | Research

Poria cocos polysaccharides exert prebiotic function to attenuate the adverse effects and improve the therapeutic outcome of 5-FU in ApcMin/+ mice

Authors: Lin Yin, Guoxin Huang, Imran Khan, Lu Su, Wenrui Xia, Betty Yuen Kwan Law, Vincent Kam Wai Wong, Qiang Wu, Jingyi Wang, Wai Kit Leong, W. L. Wendy Hsiao

Published in: Chinese Medicine | Issue 1/2022

Login to get access

Abstract

Background

As a first-line chemotherapeutic agent, 5-fluorouracil (5-FU) exhibits many side effects, weakening its efficacy in cancer treatment. In this study, we hypothesize that Poria cocos polysaccharides (PCP), a traditional Chinese herbal medicine with various bioactivities and prebiotic effects, might improve the therapeutic effect of 5-FU by restoring the homeostasis of the gut microenvironment and the commensal gut microflora.

Methods

ApcMin/+ mice were employed to evaluate the anti-cancer effect of 5-FU in conjunction with PCP treatment. Body weight and food consumption were monitored weekly. Polyp count was used to assess the anti-cancer effect of PCP and 5-FU. Expressions of mucosal cytokines and gut epithelial junction molecules were measured using qRT-PCR. 16S rRNA gene sequencing of fecal DNAs was used to evaluate the compositional changes of gut microbiota (GM). Transplantation of Lactobacillus johnsonii and Bifidobacterium animalis were performed to verify the prebiotic effects of PCP in improving the efficacy of 5-FU.

Results

The results showed that PCP treatment alleviated the weight loss caused by 5-FU treatment and reduced the polyp burden in ApcMin/+ mice. Additionally, PCP treatment eased the cytotoxic effects of 5-FU by reducing the expressions of pro-inflammatory cytokines, increasing the anti-inflammatory cytokines; and significantly improving the gut barriers by enhancing the tight junction proteins and associated adhesion molecules. Furthermore, 16S rRNA gene sequencing data showed that PCP alone or with 5-FU could stimulate the growth of probiotic bacteria (Bacteroides acidifaciens, Bacteroides intestinihominis, Butyricicoccus pullicaecorum, and the genera Lactobacillus, Bifidobacterium, Eubacterium). At the same time, it inhibited the growth of potential pathogens (e.g., Alistipes finegoldii, Alistipes massiliensis, Alistipes putredinis., Citrobacter spp., Desulfovibrio spp., and Desulfovibrio desulfuricans). Moreover, the results showed that transplantation of L.johnsonii and B.animalis effectively reduced the polyp burden in ApcMin/+ mice being treated with 5-FU.

Conclusion

Our study showed that PCP could effectively improve the anti-cancer effect of 5-FU by attenuating its side effects, modulating intestinal inflammation, improving the gut epithelial barrier, and modulating the gut microbiota of ApcMin/+ mice.
Appendix
Available only for authorised users
Literature
4.
go back to reference Hamouda N, Sano T, Oikawa Y, Ozaki T, Shimakawa M, Matsumoto K, Amagase K, Higuchi K, Kato S. Apoptosis, dysbiosis and expression of inflammatory cytokines are sequential events in the development of 5-fluorouracil-induced intestinal muco-sitis in mice. Basic Clin Pharmacol Toxicol. 2017;121(3):159–68. https://doi.org/10.1111/bcpt.12793.CrossRefPubMed Hamouda N, Sano T, Oikawa Y, Ozaki T, Shimakawa M, Matsumoto K, Amagase K, Higuchi K, Kato S. Apoptosis, dysbiosis and expression of inflammatory cytokines are sequential events in the development of 5-fluorouracil-induced intestinal muco-sitis in mice. Basic Clin Pharmacol Toxicol. 2017;121(3):159–68. https://​doi.​org/​10.​1111/​bcpt.​12793.CrossRefPubMed
5.
go back to reference Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(S9):1995–2025. https://doi.org/10.1002/cncr.20162.CrossRefPubMed Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(S9):1995–2025. https://​doi.​org/​10.​1002/​cncr.​20162.CrossRefPubMed
19.
go back to reference Justino PF, Melo LF, Nogueira AF, Costa JV, Silva LM, Santos CM, Mendes WO, Costa MR, Franco AX, Lima AA. Treatment with Saccharomyces boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in 5-fluorouracil-induced intestinal mucositis in mice. Br J Nutr. 2014;111(9):1611–21. https://doi.org/10.1017/S0007114513004248.CrossRefPubMed Justino PF, Melo LF, Nogueira AF, Costa JV, Silva LM, Santos CM, Mendes WO, Costa MR, Franco AX, Lima AA. Treatment with Saccharomyces boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in 5-fluorouracil-induced intestinal mucositis in mice. Br J Nutr. 2014;111(9):1611–21. https://​doi.​org/​10.​1017/​S000711451300424​8.CrossRefPubMed
41.
go back to reference Osman MA, Neoh H-M, Ab Mutalib N-S, Chin S-F, Mazlan L, Raja Ali RA, Zakaria AD, Ngiu CS, Ang MY, Jamal R. Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer. Sci Rep. 2021;11(1):1–12. https://doi.org/10.1038/s41598-021-82465-0.CrossRef Osman MA, Neoh H-M, Ab Mutalib N-S, Chin S-F, Mazlan L, Raja Ali RA, Zakaria AD, Ngiu CS, Ang MY, Jamal R. Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer. Sci Rep. 2021;11(1):1–12. https://​doi.​org/​10.​1038/​s41598-021-82465-0.CrossRef
45.
go back to reference Hullar MA, Burnett-Hartman AN, Lampe JW. Gut microbes, diet, and cancer. In: Zappia Vincenzo, Panico Salvatore, Russo Gian Luigi, Budillon Alfredo, Ragione Fulvio Della, editors. Advances in nutrition and cancer. Heidelberg: Springer; 2014. Hullar MA, Burnett-Hartman AN, Lampe JW. Gut microbes, diet, and cancer. In: Zappia Vincenzo, Panico Salvatore, Russo Gian Luigi, Budillon Alfredo, Ragione Fulvio Della, editors. Advances in nutrition and cancer. Heidelberg: Springer; 2014.
56.
go back to reference Fonseca W, Lucey K, Jang S, Fujimura KE, Rasky A, Ting HA, Petersen J, Johnson CC, Boushey HA, Zoratti E, Ownby DR, Levine AM, Bobbit KR, Lynch SV, Lukacs NW. Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation. Mucosal Immunol. 2017;10(6):1569–80. https://doi.org/10.1038/mi.2017.13.CrossRefPubMedPubMedCentral Fonseca W, Lucey K, Jang S, Fujimura KE, Rasky A, Ting HA, Petersen J, Johnson CC, Boushey HA, Zoratti E, Ownby DR, Levine AM, Bobbit KR, Lynch SV, Lukacs NW. Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation. Mucosal Immunol. 2017;10(6):1569–80. https://​doi.​org/​10.​1038/​mi.​2017.​13.CrossRefPubMedPubMedCentral
Metadata
Title
Poria cocos polysaccharides exert prebiotic function to attenuate the adverse effects and improve the therapeutic outcome of 5-FU in ApcMin/+ mice
Authors
Lin Yin
Guoxin Huang
Imran Khan
Lu Su
Wenrui Xia
Betty Yuen Kwan Law
Vincent Kam Wai Wong
Qiang Wu
Jingyi Wang
Wai Kit Leong
W. L. Wendy Hsiao
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Chinese Medicine / Issue 1/2022
Electronic ISSN: 1749-8546
DOI
https://doi.org/10.1186/s13020-022-00667-8

Other articles of this Issue 1/2022

Chinese Medicine 1/2022 Go to the issue