| ObjectiveHelicobacter pylori(H.pylori,Hp)is a spiral-shaped gram-negative bacterium;it is closely related to gastric mucosal damage and intestinal flora characteristics,and its induced oxidative stress may play a very important role in gastric mucosal damage.Dietary polyphenols have the effects of protecting gastric mucosa,anti-oxidation and regulating intestinal flora.Cranberry is a berry rich in multivitamins,minerals and polyphenols.A large number of studies have confirmed that it has natural antibacterial activity and strong antioxidant activity,but whether it has a certain effect on gastric mucosal damage and intestinal flora is rarely reported.The previous research of the research group focused on the effect of cranberry juice supplementation on the negative rate of Hp infection after 4 weeks of supplementation.This study intends to observe the effects of cranberry juice supplementation on gastric mucosal injury,gastric discomfort and intestinal flora changes in Hp-infected patients after 4 weeks,to compare changes in blood oxidative stress levels before and after intervention,and to analyze the relationship between the change of oxidative stress and changes in gastric mucosal damage,which providing a theoretical basis for reasonable dietary nutrition for gastric mucosal lesions in patients with Hp infection.MethodsIn this study,a randomized double-blind controlled trial was used to select study subjects according to the inclusion and exclusion criteria.Hp infected patients aged 18 to65 were randomly divided into high-dose group(27%cranberry juice 480 ml/d,Group A),low-dose group(27%cranberry juice 240 ml/d+placebo 240 ml/d,group AB),and placebo group(placebo 480 ml/d,group B).Juices and placebo have the same appearance,both in bottles(240ml/bottle)but with different numbers.The duration of intervention was 4 weeks.The basic information of the subjects was collected,and their dietary intake was collected by a 24-hour diet review method.Each subject was regularly followed up with the amount of juice and placebo used at home,checked the contents of the record card,and collected changes in stomach upset during the intervention.Some subjects were given the gastroscopy before and after the intervention.The subjects were observed the types and incidence of mucosal manifestations under gastroscopy before and after the intervention,and evaluated the endoscopic manifestations of gastric cancer-related risks according to the criteria according to the 19 endoscopic manifestations(including atrophy,diffuse redness,proliferative polyps,map-like redness,yellow tumors,and old bleeding spots,ridged redness,intestinal metaplasia,swelling of the mucous membranes,spotted redness,pitting erosion,fold enlargement/snake type,white turbid mucus,gastric polyp,punctate redness,multiple white flattening,RAC collect the regular arrangement of venous veins,goose-like skin and bulging erosion)in the Kyoto gastritis classification standard.Blood and feces samples were frozen in-80?refrigerator for blood index detection and intestinal flora analysis.The kits were used to analyze the total plasma antioxidant capacity(T-AOC),plasma 8-isoprostaglandin(8-iso-PG),malondialdehyde(MDA),superoxide dismutase(SOD),glutathione Oxidative stress indicators such as peroxidase(GSH-P_X)and catalase(CAT);inflammatory indicators such as lipopolysaccharide(LPS),tumor necrosis factor-?(TNF-?),and secreted immunoglobulin(sIgA)and other indicators.The content of serum C-reactive protein(CRP)was detected by a fully automatic biochemical analyzer.The bacterial genomic DNA was extracted from the stool samples,and the specific sequences of the V3-V4 region of the rDNA were amplified by PCR.The Illumina HiSeq platform was used for sequencing to analyze the microbial community and structure of the three groups of samples.Statistical methods such as one-way analysis of variance,paired t test,rank sum test,?2 test,and Spearman correlation analysis were used to analyze the effects of cranberry juice supplementation on gastric mucosal damage,gastric upset response,oxidative stress and inflammation in blood,changes in intestinal flora and their correlations.ResultsA total of 399 people with Hp infection were included in this study,including 246with gastric mucosal damage.Gastroscopy observations of 80 patients with Hp infection and gastric mucosal injury showed that there was no statistical difference in the incidence of gastric mucosal manifestations(19 types)between the three groups before and after intervention.There were an average of 5.23 types of gastroscopic mucosal manifestations before intervention in Group A,and an average of 5.19 after intervention(P=0.918);in Group AB there were 5.96 types before intervention,and 5.61 types after intervention(P=0.462);in Group B there were an average of 5.23 types before intervention and an average of 4.55 types after intervention(P=0.207).According to the endoscopic manifestation of gastric cancer risk in Kyoto gastritis,the average score before intervention was 2.04 points and 2.15 points after intervention(P=0.670);the group AB score was 3.52 before intervention and increased to 3.61 after intervention(P=0.780);group B had 2.10 points before intervention and scores 1.97 points after intervention(P=0.677).In addition,an analysis of the gastric discomfort during the intervention of 180Hp-infected patients with gastric mucosal lesions found that the scores based on the symptoms and severity of gastrointestinal discomfort in the study subjects showed that the median scores before and after the intervention were 0 scores(P<0.001);the median scores before intervention were both 0 in group AB(P=0.044)and in group B the median scores increased to 1 after intervention(P=0.009).During the 28-day intervention period,the average number of days of discomfort in group A(6 days)was significantly less than the number of days of discomfort in group AB(12 days)and group B(15 days)(P=0.041).The sequencing analysis results of 264 stool samples showed that Firmicutes and Bacteroides were the most dominant bacteria before and after the intervention in group A,group AB and group B,and the abundance sum before intervention was 84.68%,81.15%and 83.43%,respectively.The abundances after the intervention were 81.03%,77.10%,and 76.02%,respectively.After intervention in group A(P=0.049)and group AB(P=0.010),Bacteroides phylum were both significantly increased.And in group AB(P<0.001)and group B(P=0.023),the Firmicutes phylum were both significantly decreased after intervention.After 4 weeks of intervention,there was no statistically significant difference in the indexes of?diversity between the three groups.PCoA analysis based on binary curtis showed that the overall flora structure was scattered at the genus level before and after intervention in group A(P=0.027),while the AB group was scattered at the OTU level(P=0.053)and the genus level(P=0.072).The distribution and structure of group B were relatively compact(P>0.05).LefSe analysis showed that there were significant changes in the relative abundance of 5 bacterial genera in group A.Among them,intestinal probiotics such as Faecalibacterium and Lachnospira increased;Pseudomonas decreased significantly(all P<0.05).The relative abundance of 18 bacterial genera in the AB group was statistically significant compared with that before intervention(all P<0.05).Among them,the relative abundance of 11 genus increased,mainly due to the increase of genus such as Bifidobacterium,Blautia and Phascolarctobacterium and the decrease of genus such as Pseudomonas,Alisipes and Bilophila.After 4 weeks of intervention in Group B,only the relative abundance of Commamonas(P=0.040)and Parabacteroides(P=0.047)significantly decreased.Spearman correlation analysis showed that the number of days of bloating were negatively correlated with Lachnospira(r=-0.297,P=0.034).There was a positive correlation between the number of days of eating less and Pseudomonas(r=0.237,P=0.094).The number of days with gastric upset was positively correlated with Pseudomonas(r=0.248,P=0.080)and Ruminococcaceae UCG?002(r=0.258,P=0.068).The results of oxidative stress indicators in blood showed that after 4 weeks of intervention,compared with group B(0.34 IU/ml),T-AOC in group A increased by 1.39IU/ml(P<0.05),and group AB increased by 0.70 IU/ml.Plasma 8-iso-PG levels in groups A,AB,and B were reduced by 36.11 pg/ml,34.68 pg/ml,and 29.40 pg/ml after intervention,respectively.There was no significant difference between the three groups.After 4 weeks of intervention,the red blood cell SOD levels in group A and group AB increased by 10.44 U/mgprot and 7.23 U/mgprot,which were significantly higher than those in group B(2.05U/mgprot).Compared with before intervention,the red blood cell MDA levels in the three groups were significantly reduced after 4 weeks of intervention,but the reduction in group A(7.29nmol/mg)was significantly greater than that in group B(0.84 nmol/mg,P=0.025).After 4 weeks of intervention with cranberry juice in group A and AB,the CAT activity increased significantly,the increase was 1.44 U/mgprot and0.88 U/mgprot,respectively;group B increased 0.47 U/mgprot.However,no statistical difference was found between the three groups of GSH-PX activity before and after intervention.Analysis of blood inflammation and immune indicators showed that LPS levels increased by 0.005 ng/ml and 0.024 ng/ml respectively in group A and group AB(P<0.05),and decreased by 0.001ng/ml in group B.The level of sIgA increased by 27.42pg/ml and 73.94 pg/ml respectively in group A and AB,while the group B decreased by22.14 pg/ml after the intervention.The level of CRP increased by 0.1 mg/dL in group A,and decreased by 0.1 mg/dL in group AB.This index remained unchanged in group B.The level of TNF-?increased by 0.32 pg/ml and 0.25 pg/ml in group A and B,respectively,and decreased by 0.22 pg/ml in group AB.Moreover,it was found that the changes of the three groups of LPS,sIgA,CRP,and TNF-?indexes before and after intervention were not statistically different performed by statistical analysis.Due to the small sample size of LPS and sIgA indicators,group A and AB were combined and analyzed as the intervention group.The results showed that the LPS level in the intervention group increased significantly by 0.018 ng/ml after 4 weeks of intervention(P=0.045),while the B group decreased by 0.001 ng/ml,and there was no statistical difference between the changes in LPS levels between the two groups(P=0.447).After the intervention,the sIgA level in the intervention group increased significantly by 51.75pg/ml(P<0.05),while the B group decreased by 22.14 pg/ml,and there was no significant difference between the sIgA levels in the two groups(P=0.109).Spearman correlation analysis results showed that the red blood cell SOD was negatively correlated with the number of days of radon occurrence(r=-0.223,P=0.013),and positively correlated with Bifidobacterium(r=0.264,P=0.073).Red blood cell MDA was positively correlated with Blautia(r=0.301,P=0.040),and positively correlated with Lachnoclostridium(r=0.244,P=0.098).Plasma T-AOC was negatively related to Blautia(r=-0.268,P=0.069).ConclusionSupplementation of cranberry juice did not significantly improve gastric mucosal damage in Hp-infected patients,but it could reduce the time of gastric discomfort,reduce the level of oxidative stress in the body,and change the intestinal flora of Hp-infected patients.The improvement of gastric discomfort may be related to the reduction of oxidative stress in the body and the change of intestinal flora,but the further research is needed to verify it. |
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