Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 9;14(1):21008.
doi: 10.1038/s41598-024-71140-9.

Veillonella parvula as an anaerobic lactate-fermenting bacterium for inhibition of tumor growth and metastasis through tumor-specific colonization and decrease of tumor's lactate level

Amirhosein Kefayat  1 , Mahshid Bahrami  2 , Mojtaba Karami  3 , Soodabeh Rostami  4 , Fatemeh Ghahremani  5
Affiliations

Veillonella parvula as an anaerobic lactate-fermenting bacterium for inhibition of tumor growth and metastasis through tumor-specific colonization and decrease of tumor's lactate level

Amirhosein Kefayat et al. Sci Rep. .

Abstract

High tumor's lactate level directly associates with high tumor growth, metastasis, and patients' poor prognosis. Therefore, many studies have focused on the decrease of tumor's lactate as a novel cancer treatment. In the present study for the first time, a strictly anaerobic lactate-fermenting bacterium, Veillonella parvula, was employed for the decrease of tumor's lactate level. At first, 4T1 breast tumor-bearing BALB/c mice were administered with 106 V. parvula bacteria intravenously, orally, intraperitoneally, and intratumorally. Then, the bacteria biodistribution was evaluated. The best administration route according to tumor colonization was selected and its safety was assessed. Then, the therapeutic effect of V. parvula administration through the best route was investigated according to 4T1 murine breast tumor's growth and metastasis in vivo. In addition, histopathological and immunohistochemistry evaluations were done to estimate microscopic changes at the inner of the tumor and tumor's lactate level was measured after V. parvula administration. V. parvula exhibited considerable tumor-targeting and colonization efficacy, 24 h after intravenous administration. Normal organs were free of the bacteria after 72 h and no side effect was observed. Tumor colonization by V. parvula significantly decreased the tumors' lactate level for about 46% in comparison with control tumors which caused 44.3% and 51.6% decline (P < 0.05) in the mean tumors' volume and liver metastasis of the treatment group in comparison with the control group, respectively. The treatment group exhibited 35% inhibition in the cancer cell proliferation in comparison with the control according to the Ki-67 immunohistochemistry staining. Therefore, intravenous administration of V. parvula is a tumor-specific and safe treatment which can significantly inhibit tumors' growth and metastasis by decreasing the tumor lactate level.

Keywords: Veillonella parvula; Bacteria therapy; Breast cancer; Lactate.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Efficacy of different routes of V. parvula systemic administration according to the bacteria biodistribution and tumor colonization at the 4T1 breast tumor-bearing mice after (A) 24 h (n = 3) and (B) 72 h (n = 3) since the injection (*P˂0.05).
Fig. 2
Fig. 2
(A) Blood biochemical analysis including AST, ALT, and creatinine and (B) histopathological analyzes of the non-tumor bearing (healthy) mice (n = 5), 30 days after i.v administration of 106 V. parvula (treatment) in comparison with the control.
Fig. 3
Fig. 3
4T1 breast tumor colonization by V. parvula after i.v administration. (A) Macroscopic view of 4T1 tumors in the control and V. parvula administered tumor-bearing mice (72 h after i.v administration of 106 V. parvula, n = 5, mean tumors’ volume: 368 ± 80 mm3). Some of the tumors exhibited pus formation (Yellow arrow: pus, black arrow: tumor). (B) Low (× 4) and (C) high-power (× 100) field microscopic view of the H&E-stained sections of 4T1 breast tumors of the control and V. parvula administered groups (N: necrosis, V: viable, black arrows indicate the clustered colonies of V. parvula). The boxed regions in the panel B are viewed under high power in the panel (C). (D) High-power (× 400) field microscopic view of the central and peripheral regions of the H&E-stained sections of 4T1 breast tumors of V. parvula administered groups. The colonies of V. parvula were just observed at the central regions of the tumors and peripheral regions were bacteria free.
Fig. 4
Fig. 4
The therapeutic effects of i.v administration of V. parvula on the 4T1 breast tumors’ growth progression, metastasis, and proliferation rate. 4T1 tumor-bearing mice were i.v injected with 106 V. parvula on the 9th day after cancer cells implantation (Mean tumors volume: 109 ± 18.6 mm3). The black arrow indicates the V. parvula injection day. (A) The mean tumors’ volume progression of the control and V. parvula groups (*P < 0.05, ns: not significant). (B) The average number of metastatic colonies at 10 random high-power microscopic fields of the H&E-stained sections of the liver at the 40th day after cancer cell implantation (n = 5). (C) The high-power microscopic (× 200) field of the H&E-stained sections of liver from the control and V. parvula administered groups. The red arrows point to some of the metastatic colonies as sample. (D) The high-power microscopic (× 400) field of the immunohistochemistry Ki-67-stained sections of tumor from the control and V. parvula-treated groups. The black arrow indicates the Ki-67-positive cells as a sample.
Fig. 5
Fig. 5
Assessment of lactate level in the 4T1 breast tumors after the bacteria administration (n = 3) (*P < 0.05).
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Luo, C. et al. Global and regional trends in incidence and mortality of female breast cancer and associated factors at national level in 2000 to 2019. Chin. Med. J.135(01), 42–51 (2022). 10.1097/CM9.0000000000001814 - DOI - PMC - PubMed
    1. Ganesh, K. & Massagué, J. Targeting metastatic cancer. Nat. Med.27(1), 34–44 (2021). 10.1038/s41591-020-01195-4 - DOI - PMC - PubMed
    1. Bisoyi, P. A brief tour guide to cancer disease. In Understanding Cancer 1–20 (Elsevier, 2022).
    1. Schiliro, C. & Firestein, B. L. Mechanisms of metabolic reprogramming in cancer cells supporting enhanced growth and proliferation. Cells10(5), 1056 (2021). 10.3390/cells10051056 - DOI - PMC - PubMed
    1. Kroemer, G. & Pouyssegur, J. Tumor cell metabolism: Cancer’s Achilles’ heel. Cancer Cell13(6), 472–482 (2008). 10.1016/j.ccr.2008.05.005 - DOI - PubMed

LinkOut - more resources