Probiotic supplementation decreases intestinal transit time: Meta-analysis of randomized controlled trials

AIM: To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) and to identify factors that influence these outcomes. METHODS: A systematic review of randomized controlled trials (RCTs) of probiotic supplementation that measured ITT in adults was conducted by searching MEDLINE and EMBASE using relevant combinations. Main search limits included RCTs of probiotic supplementation in healthy or constipated adults that measured ITT. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses were conducted to examine the impact of moderator variables on ITT SMD. RESULTS: A total of 11 clinical trials with 13 treatment effects representing 464 subjects were included in this analysis. Probiotic supplementation was associated with decreased ITT in relation to controls, with an SMD of 0.40 (95%CI: 0.20-0.59, P < 0.001). Constipation (r 2 = 39%, P = 0.01), higher mean age (r 2 = 27%, P = 0.03), and higher percentage of female subjects (r 2 = 23%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation and in older vs younger subjects [both SMD: 0.59 (95%CI: 0.39-0.79) vs 0.17 (95%CI: -0.08-0.42), P = 0.01]. Medium to large treatment effects were identified with Bifidobacterium Lactis (B. lactis ) HN019 (SMD: 0.72, 95%CI: 0.27-1.18, P < 0.01) and B. lactis DN-173 010 (SMD: 0.54, 95%CI: 0.15-0.94, P < 0.01) while other single strains and combination products yielded small treatment effects. CONCLUSION: Overall, short-term probiotic supplementation decreases ITT with consistently greater treatment effects identified in constipated or older adults and with certain probiotic strains.

Irritable bowel syndrome symptom severity improves equally with probiotic and placebo

AIM To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome(IBS) symptoms and quality of life(Qo L).METHODS In this randomized triple-blind trial, adult IBS volunteerswho were recruited according to Rome Ⅲ criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk. IBS Symptom Severity Score(IBS-SSS), which constituted the primary outcome, and secondary outcomes, including individual IBS symptoms, IBS-related QoL questionnaire, anxiety and depression, defecation frequency, and stool consistency, were assessed at baseline at the end of the 8-wk runin period, after 4 and 12 wk of intervention, and after a 4-wk washout.RESULTS A total of 340 of 391 randomized volunteers completed the trial. IBS-SSS improved over 12 wk of treatment in all treatment groups, decreasing by a mean ± SD of 44.0 ± 80.2, 50.8 ± 82.4, and 48.3 ± 72.2 in the placebo, active low-dose, and active high-dose groups, respectively. Similarly, secondary outcomes did not differ between treatment groups. However, in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline(VAS > 35/100), the treatment significantly reduced the sensation of abdominal pain. Pain scores fell by 20.8 ± 22.8, 29.4 ± 17.9, and 31.2 ± 21.9 in the placebo, active low-dose, and active high-dose groups, respectively(P value for placebo vs combined active doses = 0.0460).CONCLUSION NCFM alleviates moderate to severe abdominal pain, consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression.

Comparison of bacterial quantities in left and right colon biopsies and faeces

AIM:To compare quantities of predominant and pathogenic bacteria in mucosal and faecal samples.METHODS:Twenty patients undergoing diagnostic colonoscopy with endoscopically and histologically normal mucosa were recruited to the study,14 subjects of which also supplied faecal(F) samples between 15 d to 105 d post colonoscopy.Mucosal biopsies were taken from each subject from the midportion of the ascending colon(right side samples,RM) and the sigmoid(left side samples,LM).Predominant intestinal and mucosal bacteria including clostridial 16S rRNA gene clusters Ⅳ and ⅩⅣab,Bacteroidetes,Enterobacteriaceae,Bifidobacterium spp.,Akkermansia muciniphila(A.muciniphila),Veillonella spp.,Collinsella spp.,Faecalibacterium prausnitzii(F.prausnitzii) and putative pathogens such asEscherichia coli(E.coli),Clostridium difficile(C.difficile),Helicobacter pylori(H.pylori) and Staphylococcus aureus(S.aureus) were analysed by quantitative polymerase chain reaction(qPCR).Host DNA was quantified from the mucosal samples with human glyceraldehyde 3-phosphate dehydrogenase gene targeting qPCR.Paired t tests and the Pearson correlation were applied for statistical analysis.RESULTS:The most prominent bacterial groups were clostridial groups Ⅳ and ⅩⅣa+b andBacteroidetes and bacterial species F.prausnitzii in both sample types.H.pylori and S.aureus were not detected and C.difficile was detected in only one mucosal sample and three faecal samples.E.coli was detected in less than half of the mucosal samples at both sites,but was present in all faecal samples.All detected bacteria,except Enterobacteriaceae,were present at higher levels in the faeces than in the mucosa,but the different locations in the colon presented comparable quantities(RM,LM and F followed byP 1 for RMvs F,P 2 for LMvs F andP 3 for RM vs LM:4.17 ± 0.60 log 10 /g,4.16 ± 0.56 log 10 /g,5.88 ± 1.92 log 10 /g,P 1 = 0.011,P 2 = 0.0069,P 3 = 0.9778 forA.muciniphila;6.25 ± 1.3 log 10 /g,6.09 ± 0.81 log 10 /g,8.84 ± 1.38 log 10 /g,P 1 < 0.0001,P 2 = 0.0002,P 3 = 0.6893 forBacteroidetes;5.27 ± 1.68 log 10 /g,5.38 ± 2.06 log 10 /g,8.20 ± 1.14 log 10 /g,P 1 < 0.0001,P 2 ≤ 0.0001,P 3 = 0.7535 forBifidobacterium spp.;6.44 ± 1.15 log 10 /g,6.07 ±1.45 log 10 /g,9.74 ±1.13 log 10 /g,P 1 < 0.0001,P 2 ≤ 0.0001,P 3 = 0.637 forClostridium cluster Ⅳ;6.65 ± 1.23 log 10 /g,6.57 ± 1.52 log 10 /g,9.13 ± 0.96 log 10 /g,P 1 < 0.0001,P 2 ≤ 0.0001,P 3 = 0.9317 forClostridium cluster ⅩⅣa;4.57 ± 1.44 log10/g,4.63 ± 1.34 log10/g,7.05 ± 2.48 log 10 /g,P 1 = 0.012,P 2 = 0.0357,P 3 = 0.7973 for Collinsella spp.;7.66 ± 1.50 log 10 /g,7.60 ± 1.05 log 10 /g,10.02 ± 2.02 log 10 /g,P 1 ≤ 0.0001,P 2 = 0.0013,P 3 = 0.9919 forF.prausnitzsii;6.17 ± 1.3 log 10 /g,5.85 ± 0.93 log 10 /g,7.25 ± 1.01 log 10 /g,P 1 = 0.0243,P 2 = 0.0319,P 3 = 0.6982 for Veillonella spp.;4.68 ± 1.21 log 10 /g,4.71 ± 0.83 log 10 /g,5.70 ± 2.00 log 10 /g,P 1 = 0.1927,P 2 = 0.0605,P 3 = 0.6476 forEnterobacteriaceae).TheBifidobacterium spp.counts correlated significantly between mucosal sites and mucosal and faecal samples(Pearson correlation coefficients 0.62,P = 0.040 and 0.81,P = 0.005 between the right mucosal sample and faeces and the left mucosal sample and faeces,respectively).CONCLUSION:Non-invasive faecal samples do not reflect bacterial counts on the mucosa at the individual level,except for bifidobacteria often analysed in probiotic intervention studies.

Effects of Vitamin K-1 and Menaquinone-7 on Vascular Function and Blood Pressure in Warfarin-Induced Calcification-Model in Rats

Given that vascular calcification is inversely correlated with the clinical intake of menaquinone, a rat model of warfarin-induced calcification may be useful for testing menaquinone and vitamin K-1 potential effects on vascular function. The aim of the present study was to investigate effects of vitamin K-1 and menaquinone-7 treatments on blood pressure and vascular function in warfarin-induced vascular calcification model during five-week intervention in normotensive Wistar-Kyoto rats. Blood pressure was measured weekly, and at the end of the intervention in vitro vascular reactivity measurements were done. Alizarin Red S and von Kossa stainings were used to record possible calcification of aortic sections. Routine clinical chemistry was done from serum and urine samples. Vascular calcification was seen only in a few warfarin-treated animals in histological staining. Warfarin-treatment did not change significantly blood pressure of the rats. Warfarin-treatment increased slightly the endothelium-dependent relaxation of aorta after the L-type calcium channels were blocked. Also the vascular relaxation improved after NOS inhibition in the aorta of the healthy controls and menaquinone-7 treated animals, indicating that the relaxation in those groups was not totally dependent on NO. Clinical chemistry from serum showed some differences in urea, creatinine as well as lipid and glucose metabolism between the healthy controls and warfarin-treated rats.

Contemporary meta-analysis of short-term probiotic consumption on gastrointestinal transit

AIM: To determine the efficacy of probiotic supplementation on intestinal transit time(ITT) in adults and to identify factors that influence these outcomes. METHODS: We conducted a systematic review of randomized controlled trials of probiotic supplementation that measured ITT in adults. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference(SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses examined the impact of moderator variables on SMD of ITT.RESULTS: A total of 15 clinical trials with 17 treatment effects representing 675 subjects were included in this analysis. Probiotic supplementation was moderately efficacious in decreasing ITT compared to control, with an SMD of 0.38(95%CI: 0.23-0.53, P < 0.001). Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation(SMD: 0.57 vs 0.22, P < 0.01) and in studies with high vs low study quality(SMD: 0.45 vs 0.00, P = 0.01). Constipation(R^2 = 38%, P < 0.01), higher study quality(R^2 = 31%, P = 0.01), older age(R^2 = 27%, P = 0.02), higher percentage of female subjects(R^2 = 26%, P = 0.02), and fewer probiotic strains(R^2 = 20%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Medium to large treatment effects were identified with B. lactis HN019(SMD: 0.67, P < 0.001) and B. lactis DN-173 010(SMD: 0.54, P < 0.01) while other probiotic strains yielded negligible reductions in ITT relative to control.CONCLUSION: Probiotic supplementation is moderately efficacious for reducing ITT in adults. Probiotics were most efficacious in constipated subjects, when evaluated in high-quality studies, and with certain probiotic strains.

Correcting for non-compliance when determining colonic transit time with radio-opaque markers

The use of radio-opaque markers and abdominal X-ray is the standard method for determining colonic transit time(CTT). However, when there are deviations in the intake of these markers by participants in clinical trials it is desirable to improve observations by introducingcorrections, where possible. To date, there is no standard procedure to adjust for such deviations. This report proposes a series of alternatives based on possible scenarios for deviations from the intended intake of radio-opaque markers. The proposed method to correct for missed or delayed consumption of radioopaque markers can help to increase the accuracy of the CTT measurements in clinical trials.