Background: Oxidative stress (OS) plays a crucial role in colorectal cancer (CRC) progression. Lactobacillus has been proposed as a potential modulator of OS. This randomised controlled trial aimed to evaluate the effects of Lactobacillus supplementation on OS markers and its related signalling pathways in CRC patients after surgery.
Methods: A total of 76 CRC patients were enrolled and randomised into two groups: the study group (n=39) received Lactobacillus supplementation, while the control group (n=37) received a placebo. The intervention lasted for six months following surgery. Serum levels of catalase (CAT), glutathione (GSH), oxidised glutathione (GSSG), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and F2-isoprostanes (F2-IsoPs) were measured. In addition, the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (NRF2/KEAP1), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) signalling pathways were assessed via western blot analysis.
Results: Following Lactobacillus supplementation, serum carcinoembryonic antigen (CEA) levels significantly decreased, whereas carbohydrate antigen 19-9 (CA19-9) levels remained unchanged. OS marker analysis demonstrated increased CAT, GSH, and F2-IsoPs levels and decreased GSSG and 8-oxodG levels in the study group compared to the control group. Western blot results revealed that NRF2, ASK1, MKK3, p-p38, and MKK4 protein levels were significantly reduced after Lactobacillus intervention, while KEAP1 and p-JNK remained unchanged.
Conclusions: Oral administration of Lactobacillus for six months reduced OS marker levels and inhibited NRF2/KEAP1, p38 MAPK, and JNK signalling pathways in CRC patients after surgery. These findings suggest that Lactobacillus may contribute to CRC management by modulating oxidative stress.
Metode: Ukupno 76 pacijenata sa CRC-om je nasumično podeljeno u dve grupe: studijsku (n=39), koja je dobijala Lactobacillus, i kontrolnu (n=37), koja je dobijala placebo. Intervencija je trajala šest meseci nakon operacije. Mereni su serumski nivoi katalaze (CAT), glutationa (GSH), oksidovanog glutationa (GSSG), 8-oxo-7,8-dihidro-2'-deoksigvanozina (8-oxodG) i F2-izoprostana (F2-IsoPs). Takođe su analizirani signalni putevi povezani sa NRF2/KEAP1, p38 MAPK i c-Jun N-terminalnom kinazom (JNK) primenom "western blot metode".
Rezultati: Nakon suplementacije Lactobacillus-om, nivo karcino embrionalnog antigena (CEA) u serumu bio je značajno smanjen, dok se nivo karbohidratnog antigena 19-9 (CA19-9) nije menjao. Analiza markera OS je pokazala porast nivoa CAT, GSH i F2-IsoPs, te smanjenje nivoa GSSG i 8-oxodG u studijskoj grupi u poređenju sa kontrolnom. Western blot analiza otkrila je značajno smanjenje nivoa proteina NRF2, ASK1, MKK3, p-p38 i MKK4 nakon intervencije, dok nivoi KEAP1 i p-JNK nisu pokazali značajne promene.
Zaključak: Oralna suplementacija Lactobacillus-om tokom šest meseci smanjuje markere oksidativnog stresa i inhibira NRF2/KEAP1, p38 MAPK i JNK signalne puteve kod pacijenata sa CRC-om nakon operacije. Ovi nalazi ukazuju na potencijalnu ulogu Lactobacillus-a u upravljanju kolorektalnim karcinomom kroz modulaciju oksidativnog stresa.
Keywords: JNK; Lactobacillus; NRF2; colorectal cancer; oxidative stress; p38 MAPK.
2025 Shiru Chen, Weili Ning, Jiye Zhang, Zhenting Wu, Hang Zhou, Ying Liu, published by CEON/CEES.