Open Access Active Ghrelin Leptin Bacteroidetes/ Firmicutes oo 四生gE 88°o…oo°9 5 20032 39N9=89Nzo3N=o Figure 2 Difference in the bacterial ratios and hormone levels between S1 and S3. Each symbol represents the logarithmic differential ratio of Bacteroidetes: Firmicutes(B: F)(middle), the concentration of plasma ghrelin(left), and the concentration of serum leptin(right)in a patient at S1 and S3. Symbols representing the same patients are connected with lines. P values at the bottom indicate the statistical significance according to Fisher's exact probability test. DISCUSSION (500 mg twice daily), whose dose was pretty greater Q In recent studies of gut microbiota using high-throughput than that used in the present study. Those authors also 16S rRNA gene sequencing, loss of diversity and marked observed not an increase but a decrease in the B: F ratio short-term changes in several bacterial taxa have been osteradication consistent finding after treatment with antimicrobials In the present study using H pylori-infected patients who treatment, the ecosystem of gut microbiota exhibits no S After external perturbation, such as antimicrobial were treated with first-line therapy using both amoxi- change, resilience, adaptation or failing resilience. The cillin and clarithromycin for l week, the alpha diversity robustness of the microbiota ecosystem is considered to o in the stool samples showed no significant changes at be a major factor determining which of those responses 3 months after the therapy. Given that only a slight tran- the microbiota exhibit. The difference in the age and race sient decrease in the number of bacteria was observed by between our subjects (apanese, 42-79 years of age)and a culturing method just after the therapy(see table 1), the subjects of Yap et al(Malaysian, 18-30 years of age) g the antimicrobials used in the present study might have might induced in a difference in the robustness of the 5 exerted only a moderate perturbing effect on the micro- gut microbiota ecosystem, thereby resulting in different 3 biota, thereby resulting in no marked decrease in the outcomes in the B: F ratio after antimicrobial treatment. diversity of the gut microbiota after the In addition, differences in the dose of antimicrobials s Of note, however, in the bacterial composition analysis used for eradication and the duration of follow-up might at the phylum level, the B: F ratio significantly increased also have affected the outcomes of these two studies. just after the therapy and remained increased even at Furthermore, as the subjects without H pylori infection t 8months after the therapy. Yap et al also reported that were not included in our study, it is possible that some 5 the alpha diversity was similar between pre-eradication bias due to long-lasting H. pylori infection on the B: F ratio and 6months posteradication in stool samples obtained at SI might be involved from H. pylor-infected young adults treated with When analysing the existence of any similarities in the amoxicillin(1000 mg twice daily) and clarithromycin frequency of identification among samples(see figure 3) Yanagi H, et al. BMJ Open Gastro 2017: 4: e000182 doi 10. 1136/bmjgast-2017-000187Yanagi H, et al. BMJ Open Gastro 2017;4:e000182. doi:10.1136/bmjgast-2017-000182 5 Open Access Discussion In recent studies of gut microbiota using high-throughput 16S rRNA gene sequencing, loss of diversity and marked short-term changes in several bacterial taxa have been a consistent finding after treatment with antimicrobials.17 In the present study using H. pylori-infected patients who were treated with first-line therapy using both amoxi￾cillin and clarithromycin for 1week, the alpha diversity in the stool samples showed no significant changes at 3months after the therapy. Given that only a slight tran￾sient decrease in the number of bacteria was observed by a culturing method just after the therapy (see table 1), the antimicrobials used in the present study might have exerted only a moderate perturbing effect on the micro￾biota, thereby resulting in no marked decrease in the diversity of the gut microbiota after the therapy. Of note, however, in the bacterial composition analysis at the phylum level, the B:F ratio significantly increased just after the therapy and remained increased even at 3months after the therapy. Yap et al18 also reported that the alpha diversity was similar between pre-eradication and 6months posteradication in stool samples obtained from H. pylori-infected young adults treated with amoxicillin (1000mg twice daily) and clarithromycin (500mg twice daily), whose dose was pretty greater than that used in the present study. Those authors also observed not an increase but a decrease in the B:F ratio posteradication. After external perturbation, such as antimicrobial treatment, the ecosystem of gut microbiota exhibits no change, resilience, adaptation or failing resilience.19 The robustness of the microbiota ecosystem is considered to be a major factor determining which of those responses the microbiota exhibit. The difference in the age and race between our subjects (Japanese, 42–79 years of age) and the subjects of Yap et al (Malaysian, 18–30 years of age) might induced in a difference in the robustness of the gut microbiota ecosystem, thereby resulting in different outcomes in the B:F ratio after antimicrobial treatment. In addition, differences in the dose of antimicrobials used for eradication and the duration of follow-up might also have affected the outcomes of these two studies. Furthermore, as the subjects without H. pylori infection were not included in our study, it is possible that some bias due to long-lasting H. pylori infection on the B:F ratio at S1 might be involved. When analysing the existence of any similarities in the frequency of identification among samples (see figure 3), Figure 2 Difference in the bacterial ratios and hormone levels between S1 and S3. Each symbol represents the logarithmic differential ratio of Bacteroidetes:Firmicutes (B:F) (middle), the concentration of plasma ghrelin (left), and the concentration of serum leptin (right) in a patient at S1 and S3. Symbols representing the same patients are connected with lines. P values at the bottom indicate the statistical significance according to Fisher’s exact probability test. copyright. on 4 July 2018 by guest. Protected by http://bmjopengastro.bmj.com/ BMJ Open Gastroenterol: first published as 10.1136/bmjgast-2017-000182 on 26 November 2017. Downloaded from