Effect Of Preventive Application Of Lactobacillus Reuteri DSM 17938 On Visceral Pain Sensitivity And Expression Of TRPV1 In Colonic Mucosa Of Early Life Antibiotic Exposured Rats

Objective: To investigate the effect of preventive application of Lactobacillus returi(LR)DSM 17938 on visceral pain sensitivity and the expression of transient receptor potential vanilloid-1(TRPV1)in colonic mucosa in rats exposed to antibiotics in the early life.Methods: A total of 18 newborn SD rats were randomly divided into 3 groups(n=6,respectively),the antibiotic exposure group(Group A),the probiotic intervention group(Group B)and the control group(Group C).From postnatal day 2(PND2)to PND6,rats in group A were given ceftriaxone by gavage.And normal saline was given after 2hours by gavage.Rats in the group B were given ceftriaxone by gavage at the same time but 2 hours later they were given Lactobacillus returi(LR)DSM 17938 by gavage.Rats in group C were given normal saline by gavage twice a day.At PND42,visceral pain sensitivity of rats were evaluated by abdominal withdrawal reflex(AWR)score and the discharge radiation value of external oblique muscle of abdomen stimulated by colorectal distension(CRD).Then the colon tissues of rats were observed under the microscope.Immunohistochemical staining was used to compare the expression difference of TRPV1 in colon mucosa of rats.SPSS 22.0 software was used for statistical analysis,and α=0.05 was the significance test standard.Results: In PND2,PND7,PND21 and PND42,there was no significant difference in body weight among the three groups(P>0.05).When the CRD stimulation pressure was 40 mm Hg,the AWR scores of Group A,Group B and Group C were 2.95±0.13,2.17±0.28 and 1.95±0.13 respectively.And when the CRD stimulation pressure was60 mm Hg,the AWR scores of Group A,Group B and Group C were 3.95±0.13,3.17±0.28 and 2.95±0.13 respectively.The AWR score of Group A was significantly higher than other groups(P<0.05).There was no significant difference in AWR score between Group B and Group C(P > 0.05).In PND42,the pain thresholds of rats in Group A,Group B and Group C were 43.33±8.16 mm Hg,60.00±0.00 mm Hg and63.33±8.16 mm Hg.The pain thresholds of rats in Group A were significantly higher than other groups(P<0.05).And there was no significant difference between Group B and Group C(P>0.05).When the CRD stimulation pressure was 40 mm Hg,the discharge radiation value of external oblique muscle of abdomen of Group A,Group B and Group C were 197.92±40.84%,132.55±20.67% and 90.22±21.13% respectively.And when the CRD stimulation pressure was 60 mm Hg,the discharge radiation value of external oblique muscle of abdomen of Group A,Group B and Group C were 267.53±67.80%,191.15±45.56% and 131.49±29.55% respectively.The discharge radiation value of external oblique muscle of abdomen of Group A was significantly higher than the other groups(P < 0.05).And the discharge radiation value of external oblique muscle of abdomen of Group B was significantly higher than Group C(P < 0.05).The average optical density value(AO value)of TRPV1 in colon mucosa tissue of rats of Group A,Group B and Group C were 0.095±0.028,0.037±0.008 and 0.055±0.013 respectively.The average optical density value(AO value)of TRPV1 in colon mucosa tissue of rats of Group A was significantly higher than the other groups(P<0.05).And there was no significant difference between Group B and Group C(P>0.05).Conclusions: Early life antibiotic exposure could lead to hypersensitivity in SD rats during the development period with high expression of TRPV1 in colon mucosa increases.Preventive application of LR DSM 17938 could correct the change and promoted visceral pain sensitivity and the expression of TRPV1 in colon mucosa to normal level.