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Showing papers by "Arthur C. Ouwehand published in 2017"


Journal ArticleDOI
TL;DR: Patients with colon cancer harbour a distinct microbiota signature in the tumour tissue and nearby mucosa, which was altered with probiotic intervention, and results show promise for potential therapeutic benefits in CRC by manipulation of the microbiota.
Abstract: Objective The colonic microbiota is altered in patients with colorectal cancer (CRC). We investigated the microbiota composition of patients with colon cancer compared with controls devoid of neoplastic or inflammatory disease and the potential to modify the colonic microbiota with probiotics. Design Biopsy samples were obtained from the normal mucosa and tumour during colonoscopy from 15 patients with colon cancer. Subsequent patient-matched samples were taken at surgery from the tumour and nearby mucosa from the patients with cancer, eight of whom had received two daily tablets totalling 1.4×1010 CFUs Bifidobacterium lactis Bl-04 and 7×109 CFUs Lactobacillus acidophilus NCFM. Faecal samples were obtained after colonoscopy prior to starting the intervention and at surgery. In addition, 21 mucosal biopsies from non-cancer controls were obtained during colonoscopy followed by later faecal samples. The colonic and faecal microbiota was assessed by 16S rRNA gene amplicon sequencing. Results The tumour microbiota was characterised by increased microbial diversity and enrichment of several taxa including Fusobacterium, Selenomonas and Peptostreptococcus compared with the control microbiota. Patients with colon cancer that received probiotics had an increased abundance of butyrate-producing bacteria, especially Faecalibacterium and Clostridiales spp in the tumour, non-tumour mucosa and faecal microbiota. CRC-associated genera such as Fusobacterium and Peptostreptococcus tended to be reduced in the faecal microbiota of patients that received probiotics. Conclusions Patients with colon cancer harbour a distinct microbiota signature in the tumour tissue and nearby mucosa, which was altered with probiotic intervention. Our results show promise for potential therapeutic benefits in CRC by manipulation of the microbiota. Trial registration number NCT03072641; Results.

236 citations


Journal ArticleDOI
Arthur C. Ouwehand1
TL;DR: The findings are very compelling; both meta-analyses and dedicated dose-response studies observe a positive correlation between dose and AAD risk, and studies comparing two or more doses indicate that faecal recovery and risk reduction of AAD follow a positive dose- response relationship.
Abstract: The probiotic definition requires the administration of an ‘adequate amount’ in order to obtain a health benefit. What that amount should be is not indicated. Here, an overview is given of studies that investigated the dose-response relation of probiotics in human interventions. Studies were divided in; meta-analyses, meta-analyses on specific probiotic strains, and studies testing two or more doses of a probiotic (combination) in the same study. Meta-analyses on the effect of probiotics on antibiotic associated diarrhoea (AAD) suggest a dose-response effect; for Clostridium difficile-associated diarrhoea on the other hand no dose-response was observed. For other end-points; such as necrotising enterocolitis, prevention of atopic dermatitis and slow intestinal transit, no dose-response relation was identified in meta-analyses. For prophylaxis in colorectal cancer and relief of irritable bowel syndrome, no dose-response relation was determined. However, for blood pressure, a meta-analysis observed that hig...

136 citations


Journal ArticleDOI
TL;DR: In this article, the authors conducted a systematic review of randomized controlled trials that measured weekly stool frequency or ITT in constipated adults receiving probiotic-containing supplements and found that supplementing with products containing Lactobacillus or Bifidobacterium species increases stool frequency and reduces ITT.
Abstract: Background Probiotics are commonly recommended for the alleviation of constipation symptoms. The aim of this research was to determine the effects of probiotic-containing products on stool frequency and intestinal transit time (ITT) in constipated adults and to determine the factors that influence the efficacy of these products. Methods We conducted a systematic review of randomized controlled trials that measured weekly stool frequency or ITT in constipated adults receiving probiotic-containing supplements. A random effects meta-analysis was performed; stool frequency was summarized by the mean difference statistic and ITT was summarized by the standardized mean difference (SMD) statistic. Meta-regression and diagnostic model performance testing were used to identify publication bias and sources of heterogeneity. Results A total of 21 studies (23 comparisons) comprising 2656 subjects were included. All studies utilized probiotics containing Lactobacillus or Bifidobacterium species. Probiotic-containing products resulted in a mean increase in weekly stool frequency of 0.83 (95% confidence interval [CI] 0.53-1.14, P<0.001). There was high heterogeneity among the studies (I2=85%, P<0.001) and evidence of significant publication bias (Egger’s P-value <0.01). After adjustment for publication bias, the mean difference in weekly stool frequency was reduced from 0.83 to 0.30. The effects on stool frequency were greater in studies where functional constipation was diagnosed using Rome III (P<0.01), or Rome II or III criteria (P<0.05), compared to non-Rome diagnosis techniques. Probiotic-containing products were also efficacious in reducing ITT (SMD=0.65, 95%CI 0.33-0.97, P<0.001). There was high heterogeneity among studies (I2=66%, P<0.01), but no evidence of publication bias (Egger’s P-value=0.52). A larger total sample size was associated with greater efficacy as regards ITT (P=0.03). The probiotic species, the number of probiotic strains and the daily probiotic dosage had no influence on the outcomes. Conclusion Supplementation with products containing Lactobacillus or Bifidobacterium species increases stool frequency and reduces ITT in constipated adults. However, since significant heterogeneity in outcomes was detected among the studies analyzed, the results should be interpreted with caution. Keywords Constipation, meta-analysis, probiotic, stool frequency, transit time Ann Gastroenterol 2017; 30 (6): 629-639

53 citations


Journal ArticleDOI
TL;DR: These findings demonstrate a comprehensive approach of in vitro, in silico, and in vivo safety testing for probiotics and reveal no bacterial toxin genes known to harm mammalian hosts in any of the strains.

37 citations


Journal ArticleDOI
TL;DR: The gut bacterial community structure in 13–14-year-old Indian and Finnish children differs significantly, and a strong influence of FUT2 and birth mode variants on specific gut bacterial taxa was noticed to differ between the two populations under study.
Abstract: The human gut microbiome plays a crucial role in the compositional development of gut microbiota. Though well documented in western pediatrics population, little is known about how various host conditions affect populations in different geographic locations such as the Indian subcontinent. Given the impact of distinct environmental conditions, our study assess the gut bacterial diversity of a small cohort of Indian and Finnish children and investigated the influence of FUT2 secretor status and birth mode on the gut microbiome of these populations. Using multiple profiling techniques, we show that the gut bacterial community structure in 13–14-year-old Indian (n = 47) and Finnish (n = 52) children differs significantly. Specifically, Finnish children possessed higher Blautia and Bifidobacterium, while genera Prevotella and Megasphaera were predominant in Indian children. Our study also demonstrates a strong influence of FUT2 and birth mode variants on specific gut bacterial taxa, influence of which was noticed to differ between the two populations under study.

35 citations


Journal ArticleDOI
TL;DR: In this article, Lactobacillus paracasei Lpc-37 or Bifidobacterium lactis HN019 by 2-5-year-old children was found to reduce risk for diarrhoea and fever during the rainy season.
Abstract: ​Background: Consumption of Lactobacillus paracasei Lpc-37 or Bifidobacterium lactis HN019 by 2–5-year-old children was found to reduce risk for diarrhoea and fever during the rainy season.Objective: Can changes in faecal short chain fatty acids (SCFAs) or branched chain fatty acids (BCFAs) explain the observed positive influence of probiotics and their role on nutritional status and diarrhoea risk?Design: Faecal samples were analysed for SCFAs and BCFAs and correlated to Bifidobacterium and Lactobacillus levels; both at the start and after nine months’ consumption of either of the two probiotic strains, or placebo.Results: No differences in SCFAs, BCFAs, Lactobacillus or Bifidobacterium levels were found between boys and girls. Severely underweight children were observed to have the highest Lactobacillus levels. Probiotic intervention was found to be associated with higher levels of selected SCFAs and BCFAs in subjects who had experienced diarrhoea. Treatment with either of the probiotics led to ...

26 citations


Journal ArticleDOI
31 Aug 2017
TL;DR: Overall, in adults diagnosed with functional constipation per Rome III criteria, significant heterogeneity in CTT, PAC-SYM, and PAC-QOL exists among studies, and Variability among studies may be explained by geography and patient factors.
Abstract: Availability of normative patient outcome data may assist in designing experiments and estimating sample sizes. The purpose of this review was to determine normative ranges for colonic transit time (CTT), Patient Assessment of Constipation-Symptoms (PAC-SYM), and Patient Assessment of Constipation-Quality of Life (PAC-QOL) in adults diagnosed with functional constipation per Rome III guidelines. Pooled estimates were derived from random-effects meta-analysis. Meta-regression was used to explore sources of heterogeneity among studies. A total of 24 studies (3786 patients) were included in the review. In 10 studies with 1119 patients, pooled CTT was 58 hours (95% confidence interval [CI]: 50-65 hours). Publication bias was not evident (Egger P = .51); heterogeneity was high ( I 2 = 92%, P P = .44). Heterogeneity was high ( I 2 = 90%, P P = .28); heterogeneity was high ( I 2 = 98%, P

18 citations


Journal ArticleDOI
TL;DR: It can be concluded that probiotics do not have an antagonistic effect on each other’s survival when used in a multi-strains product compared to a single-strain product, at least within a microbiota in a simulated colonic environment.
Abstract: Background: Probiotic formulations can be single- or multi-strain. Commercially, multi-strain preparations have been suggested to have improved functionality over single-strain cultures. Probiotics are often tested as single-strain preparations but may subsequently be commercially formulated as multi-strain products. Objective: The aim of this study was to determine what happens at the site of action, the intestine, with probiotics as single- compared to multi-strain preparations. The human gastrointestinal tract contains a broad mixture of different microbes which may affect the survival of different probiotics in different ways. Design: The current study was performed to evaluate, in an in vitro colon simulation, whether probiotics influence each other's survival when they are taken as a combination of several strains (HOWARU Restore; Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium lactis Bl-04 and B. lactis Bi-07) compared to the strains as single preparations. Results: All strains could be detected after the colon simulations and there were no substantial differences in levels of the same strain when comparing single- and multi-strain products. Conclusions: It can be concluded that probiotics do not have an antagonistic effect on each other's survival when used in a multi-strain product compared to a single-strain product, at least within a microbiota in a simulated colonic environment.

18 citations


Journal ArticleDOI
TL;DR: In this study, a dental simulator was used to determine the effects of commercial sucrose and xylitol mint products on the adherence and planktonic growth of Streptococcus mutans.
Abstract: Few laboratory methods exist for evaluating the cariogenicity of food ingredients. In this study, a dental simulator was used to determine the effects of commercial sucrose and xylitol mint products on the adherence and planktonic growth of Streptococcus mutans. Solutions (3% w/v) of sucrose, xylitol, sucrose mints, xylitol mints, xylitol with 0.02% peppermint oil (PO), and 0.02% PO alone were used to test the levels of planktonic and adhered S. mutans. A dental simulator with continuous artificial saliva flow, constant temperature, and mixing was used as a test environment and hydroxyapatite (HA) discs were implemented into the model to simulate the tooth surface. Bacterial content was quantified by qPCR. Compared with the artificial saliva alone, sucrose and sucrose mints increased the numbers of HA-attached S. mutans, whereas xylitol decreased them. Similarly, planktonic S. mutans quantities rose with sucrose and declined with xylitol and xylitol mints. Versus sucrose mints, xylitol mints significantly reduced the counts of HA-bound and planktonic S. mutans. Similar results were observed with the main ingredients of both types of mints separately. PO-supplemented artificial saliva did not influence the numbers of S. mutans that attached to HA or planktonic S. mutans compared with artificial saliva control. In our dental simulator model, xylitol reduced the counts of adhering and planktonic S.mutans. The mints behaved similarly as their pure, main ingredients—sucrose or xylitol, respectively. PO, which has been suggested to have antimicrobial properties, did not influence S. mutans colonization.

14 citations


Journal ArticleDOI
TL;DR: The results show that in vivo models are needed to reliably assess the digestibility of α-glycosidic-linked oligomeric dietary fibre candidates, possibly due to absence of brush border α-glucosidase activity in the current in vitro assessment.
Abstract: The aim was to develop novel fibres by enzymatic synthesis, to determine their total dietary fibre by AOAC method 2009.01 and to estimate their potential digestibility and assess their digestibility in vivo using glycaemic and insulinaemic responses as markers in mice and randomised clinical trial models. We found that fibre candidates to which α-(1,2) branching was added were resistant to digestion in the mouse model, depending on the amount of branching. These results show that in vivo models are needed to reliably assess the digestibility of α-glycosidic-linked oligomeric dietary fibre candidates, possibly due to absence of brush border α-glucosidase activity in the current in vitro assessment. α-(1,3)-linked and α-(1,6)-linked glucose oligomers were completely digested in humans and mice. In conclusion, it is possible to develop dietary soluble fibres by enzymatic synthesis. Adding α-(1,2) branching increases their resistance to digestion in vivo and can thus improve their suitability as potential fibre candidates. Clinical Trial Registry: ClinicalTrials.gov, NCT02701270.

10 citations


Journal ArticleDOI
TL;DR: The proposed method to correct for missed or delayed consumption of radio-opaque markers can help to increase the accuracy of the CTT measurements in clinical trials.
Abstract: 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 introducing corrections, 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 radio-opaque markers can help to increase the accuracy of the CTT measurements in clinical trials.