Long term exposure to antibiotics is one of the most common causes of intestinal microbiota imbalance. Dysfunction of intestinal flora can lead to many diseases, such as inflammatory bowel disease, type 1 diabetes, irritable bowel syndrome, obesity, metabolic syndrome, cancer, non-alcoholic fatty liver and non-alcoholic steatohepatitis, etc. The gut brain axis plays an important role in bodily functions such as metabolism, food intake, glucose regulation, and insulin sensitivity, and also plays a crucial role in maintaining central nervous system homeostasis, as well as regulating emotions and cognitive behavior. The bidirectional connection between the hippocampus and the medial temporal lobe of the brain helps with learning and recognition function, and the reduction of beneficial gut microbiota can lead to changes in cognitive ability.
Vitamin K2 is mainly produced by gut microbiota, meeting 50% of daily vitamin K requirements. Vitamin K2 can improve the gut microbiota and is associated with the central nervous system, which is closely related to mental disorders, through the gut brain axis.
In October 2023, Chatterjee et al. published "Neuroprotective effect of vitamin K2 on cognitive decline related to intestinal microbiota imbalance" in the journal Physiology&Behavior. Conclusion: Research has shown that vitamin K2 (MK-7) can improve beneficial gut microbiota, reduce inflammation and oxidative stress reactions in the gut and central nervous system, thereby reversing antibiotic mediated hippocampal neuronal loss and preventing cognitive decline related to gut microbiota imbalance.
1.Research methods
Grouping: 24 Swiss albino mice were randomly divided into 4 groups:
①Control group (6 animals):
Oral administration of 2% Tween 80 by gavage for a total of 3 weeks;
②Microbial dysbiosis group (6 animals):
Oral administration of ampicillin sodium (250mg/kg/d) by gavage for a total of 2 weeks;
③Microbial imbalance+vitamin K2 treatment group (6 animals):
Oral administration of ampicillin sodium (250mg/kg/d) by gavage and treatment with vitamin K2 (MK-7) (0.05mg/kg/d) for a total of 3 weeks;
④Vitamin K2 group (6 animals):
Oral administration of vitamin K2 (MK-7) (0.05mg/kg/d) by gavage for a total of 3 weeks.
Observation indicators:
①Compare the results of treatment with or without vitamin K2;
②After completing the administration, on the 21st day, the feces of mice were collected for determination of lactic acid bacteria, bifidobacteria, Firmicutes, and Clostridium, and the relative values were compared with all bacteria;
③Behavioral ability research: Elevated maze (EPM), passive avoidance test (PAT), Morris water maze (MWM), and novel object recognition (NOR) to measure cognitive ability;
④Assess inflammation in the brain and colon: measure the amount of AchE activation, myeloperoxidase (MPO) activity, and cholinergic neurotransmitter levels in the hippocampus of the cerebral cortex;
⑤Effects of antibiotics and vitamin K2: Determination of histopathological changes in intestinal villus structure, hippocampal neurons, hippocampus, and intestine.
2.Research results
2.1 The effect of vitamin K2 on the gut microbiota
Compared with the control group (Control), the relative amounts of (A) lactic acid bacteria, (B) bifidobacteria, (C) Firmicutes, and (D) Clostridium in the antibiotic treatment group (Anb) decreased. The relative amount of bacteria in the group receiving antibiotic+vitamin K2 treatment (Anb+Vit K2) significantly increased (p<0.01).
2.2 The impact of vitamin K2 on cognition
Compared with the control group (Control), the antibiotic treatment group (Anb) showed a decrease in (A) hypotension delay, (B) transmission delay, and (C) preference index. The treatment group receiving antibiotics and vitamin K2 (Anb+Vit K2) showed a significant increase (p<0.05).
2.3 The effect of vitamin K2 on acetylcholinesterase (AchE) activity and reduced glutathione (GSH)
(A) Compared with the control group (Control), the GSH level in the antibiotic treated group (Anb) significantly decreased (p<0.01). The group receiving antibiotic+vitamin K2 treatment (Anb+Vit K2) showed a significant increase (p<0.001). (B) Compared with the control group (Control), the antibiotic treatment group (Anb) showed a significant increase in brain AchE activity (p<0.01). The AchE activity in the brain of the group receiving antibiotic+vitamin K2 treatment (Anb+Vit K2) was significantly reduced (p<0.05).
2.4 The effect of vitamin K2 on brain malondialdehyde (MDA) and superoxide dismutase (SOD)
(A) Compared with the control group (Control), the MDA level in the antibiotic treated group (Anb) significantly increased (p<0.001). The MDA levels in the group receiving antibiotic+vitamin K2 treatment (Anb+Vit K2) were significantly reduced (p<0.001). (B) Compared with the control group (Control), the antibiotic treatment group (Anb) showed a significant decrease in brain SOD (p<0.001). The brain SOD of the group receiving antibiotic+vitamin K2 treatment (Anb+Vit K2) significantly increased (p<0.01).
2.5 The effect of vitamin K2 on myeloperoxidase activity (MPO, a biomarker of inflammation and oxidative stress) and FITC glucan levels (intestinal permeability)
(A) Compared with the control group (Control), the antibiotic treatment group (Anb) showed a significant increase in brain MPO activity (p<0.001). The brain MPO activity in the group receiving antibiotic+vitamin K2 treatment (Anb+Vit K2) was significantly reduced (p<0.001). (B) Compared with the control group (Control), the antibiotic treatment group (Anb) showed a significant increase in colonic MPO activity (p<0.01). The colon MPO activity in the group receiving antibiotic+vitamin K2 treatment (Anb+Vit K2) was significantly reduced (p<0.01). (C) Compared with the control group (Control), the plasma FITC glucan levels in the antibiotic treated group (Anb) were significantly increased (p<0.001). The plasma FITC glucan levels in the group receiving antibiotic+vitamin K2 treatment (Anb+Vit K2) were significantly reduced (p<0.001).
2.6 The effect of vitamin K2 on intestinal villus length and crypt depth
① The histopathological examination of intestinal slices showed that (A) the control group; (B) Antibiotic treatment group; (C) The group receiving antibiotics and vitamin K2 treatment; (D) Measurement of villus length and crypt depth.
② The comparison results showed that compared with the control group, the length and depth of intestinal villi in the antibiotic treatment group were significantly shortened (p<0.001), while the group receiving antibiotic+vitamin K2 treatment significantly increased (p<0.001).
2.7 The effect of vitamin K2 on hippocampal neurons
The histopathological examination of hippocampal slices showed a significant decrease in the number and density of neurons in the CA1 and CA3 regions of the hippocampus in the antibiotic treated group (Anb) compared to the control group (Control). The number and density of neurons in the group receiving antibiotic+vitamin K2 treatment (Anb+Vit K2) significantly increased.
3.Research conclusion
Vitamin K2 can improve beneficial gut microbiota, reduce inflammation and oxidative stress in the gut and central nervous system, thereby reversing antibiotic mediated hippocampal neuronal loss and preventing cognitive decline related to gut microbiota imbalance.
Vitamin K2 (MK-7) is a recognized antioxidant commonly used to improve bone health and prevent arterial calcification. Current research has shown that vitamin K2 (MK-7) can also protect and combat cognitive decline caused by intestinal microbiota imbalance.
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