OBJECTIVE

2

To investigate ameliorative effects and mechanisms of two probiotics （

Bacillus subtilis

，

Lactobacillus acidophilus

） combined with Aurantii Fructus Immaturus （AFI） on functional dyspepsia （FD） in rats.

METHODS

2

Rats were randomly divided into blank group， model group， positive control group （domperidone group， 2.7 mg/kg）， AFI group （9 g/kg），

L. acidophilus

group （5×10

7

cfu/kg），

B. subtilis

group （5×10

7

cfu/kg），

L. acidophilus

+ AFI group （

L. acidophilus

5×10

7

cfu/kg+AFI 9 g/kg）， and

B. subtilis

+AFI group （

B. subtilis

5×10

7

cfu/kg+AFI 9 g/kg）， with 8 rats in each group. Except for the blank group， FD model was established by tail-clamping stimulation+hunger and satiety disorder+swimming exhaustion in other groups. After model

ing， each group was given the corresponding drug/probiotic suspensions/physiological saline intragastrically， once a day， for 14 consecutive days. After the last medication， gastric emptying rate and the rate of propulsion of the small intestine in rats were measured； the levels of brain-gut peptide-related indicators [gastrin （GAS）， substance P （SP）， vasoactive intestinal peptide （VIP）， somatostatin （SS） and cholecystokinin （CCK）

]

in the serum of rats were measured. The pathological morphology of the gastric antrum tissue and duodenal tissue was observed. Cecal contents from the rats were collected for gut microbiota sequencing analysis. The protein expression levels of tyrosine kinase receptor c-Kit and stem cell factor （SCF） in the gastric antrum tissue， as well as Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor κB （NF-κB） in the duodenal tissue of the rats were detected.

RESULTS

2

Compared with the blank group， model group showed significantly lower gastric emptying rate， small intestinal propulsion rate， serum levels of GAS and SP， relative abundance of Firmicutes， Ace， Chao and Sobs indexes of the gut microbiota， and protein levels of SCF and c-Kit in gastric antrum （

P

＜0.05）， while serum levels of VIP， SS and CCK， relative abundance of Bacteroidetes， as well as protein expressions of TLR4， MyD88， and NF-κB， were significantly higher （

P

＜0.05）. The histological structure of the gastric antrum tissue appeared basically normal； however， abnormalities were observed in the duodenal structure， with a significant infiltration of inflammatory cells visible. Compared with the model group， all treatment groups significantly modulated most of the above indexes （

P

＜0.05）. The histological structure of the gastric antrum tissue was normal. Except for the

B. subtilis

group and the

B. subtilis

+AFI group， the pathological states of the duodenum in the remaining rats grad

ually recovered. Compared with each single drug group， most of above indexes in rats from each combination group showed further improvement （

P

＜0.05）.

CONCLUSIONS

2

The combination of AFI with two probiotics can improve gastrointestinal motility in FD rats， and the effect is superior to that of using the drugs alone. The specific underlying mechanisms may be related to the activation of the SCF/c-Kit signaling pathway and the inhibition of the TLR4/MyD88/NF-κB signaling pathway.