Systematic review and meta-analysis: the effects of fermented milk with Bifidobacterium lactis CNCM I-2494 and lactic acid bacteria on gastrointestinal discomfort in the general adult population

Eales, J., Gibson, P., Whorwell, P., Kellow, et al. (2016). Therapeutic Advances in Gastroenterology, 1756283X16670075.

http://tag.sagepub.com/content/early/2016/10/06/1756283X16670075.abstract

Background

Probiotics have been widely studied in the context of human health and have been suggested as potentially beneficial in preventing infections and treating conditions such as the common cold and a variety of gastrointestinal (GI) disorders such as inflammatory bowel disease, irritable bowel syndrome, constipation, and acute and antibiotic-associated diarrhoea.

Study objective

This review aimed to evaluate the effectiveness of a probiotic fermented milk containing a specific mix of Bifidobacterium lactis (B.lactis) CNCM 1-2494 and four lactic acid bacteria (Lactobacillus bulgaricus strains CNCM I-1632 and CNCM I-1519, Streptococcus thermophilus strain CNCM I-1630, and Lactococcus lactis ssp. lactis strain CNCM I-1631) on GI discomfort in the general adult population.

Study design

A systematic review and meta-analysis was carried out according to the Cochrane Handbook for Systematic Reviews. The protocol was registered on the PROSPERO database. The population of interest was adults with gastrointestinal discomfort. Studies of individuals with GI conditions including IBS, Crohn’s disease, ulcerative colitis, pouchitis, coeliac disease, colon cancer, constipation, diarrhoea or true healthy participants free from GI symptoms were excluded. Study designs eligible for inclusion were prospective, double blind, randomised controlled trials of at least 4 weeks duration. Probiotic interventions could be of any dose as long as they comprised the specified mix of interest but interventions combining other functional ingredients such as prebiotics or vitamins were excluded. Acceptable control products included non-fermented dairy products which lacked probiotics (if of the same taste, colour and appearance); heat-treated active products or other fermented milk products without ‘active’ probiotics. Eligible outcome measures were changes in gastrointestinal comfort measured by an overall assessment using a single integrated question with a dichotomous outcome (classifying each participant as a responder or nonresponder) or a composite score comprising at least two of the following individual digestive symptoms: abdominal pain/discomfort; abdominal pain; bloating; borborygmi (rumbling); or flatulence. Study quality was assessed using criteria based on the Cochrane risk of bias tool. Individual patient data from these studies were used to carry out a meta-analysis based on an intention-to-treat population using random effects models.

Main findings:

Thirty seven full text articles were assessed out of a total of 12,444 identified records. Three human studies with a total of 598 subjects were included in the analysis (Donazzolo et al. 2007, Guyonnet et al. 2009; Marteau et al. 2013). All trials provided 2 x 125 g daily doses of the same intervention product (containing B.lactis CNCMI-2494 (1.25 x 1010 colony forming units per pot) and S.thermophilus and L.bulgaricus (1.2 x 109 colony forming units per pot) for a duration of four weeks. All three studies were rated as having a low risk of bias.

Overall, 52% of subjects in the intervention group were classed as responders vs. 42% in the control group and 6% of subjects in the intervention group reported deterioration in GI well-being vs. 12% in the control group. There was a significant effect in favour of probiotic fermented milk in terms of overall Gl discomfort/well-being with no significant heterogeneity between studies. The overall estimated odds ratio for a response was 1.48 (95% CI 1.07 to 2.05), meaning that an individual was 48% more likely to be a responder after consuming the intervention vs. the control. The number needed to treat (an estimate of how many people need to receive a treatment before one person would experience a beneficial outcome) was calculated to be 10.24.

There was a significant effect in favour of the intervention in relation to the composite score of digestive symptoms (estimated standardised mean difference (SMD) -0.21 (95% CI -0.37 to -0.05)). Exploratory analysis revealed that the lower the symptom score, the higher the probability of a response.

Limitations of the study

The vast majority (96.5%) of the study population included in this analysis were female; therefore these results may not be applicable to men. A strength of the analysis is that only 1.2% of the data could not be included (as it was not possible to calculate responder status for a small proportion of the subjects) therefore the total number of subjects was fairly large. In addition, the inclusion of studies of identical design, intervention product, dose and treatment duration means that firm conclusions can be drawn about this specific mix and dose of probiotics. However, it is important to note that one of the included studies was a research centre report which is not published in a peer-reviewed journal.

Author conclusions

The magnitude of effect reported in this analysis (SMD -0.21) is similar to those reported for other probiotics and improvements in GI outcomes (Ford et al. 2014). Similarly, the rate of responders (OR=1.48), NNT (10.24) and difference in responder rate (9.7%) values are similar to reported improvements in global IBS symptoms after treatment with the antibiotic rifaximin (OR 1.57; NNT 10.2; difference in responder rate 9.8%; Menees et al. 2012). The significant improvements in GI symptoms noted in this analysis were consistent across all three studies. The authors concluded that daily consumption of probiotic fermented milk with B.lactis CNCM I-2494 and lactic acid bacteria is likely to offer significant benefit to healthy individuals experiencing mild GI symptoms but who do not have a medical diagnosis, though those with worse symptoms did not respond as well.

Wider research context

The effects of probiotics are thought to be both species and strain-specific and therefore pooling data derived from studies using identical strains or mixtures of strains, as in the present study, is much more useful in ascertaining any health effects than meta-analyses which group different probiotics together. In a recent meta-analysis examining the effect of probiotics on GI transit time in adults (Miller 2016), subgroup analysis revealed two strains of B.lactis (HN019 and DN-173 010) to be more efficacious than B.lactis BB12, L.casei CRL 431 and L.rhamnosus GG.

Relevance

Probiotics appear to be safe in healthy individuals and furthermore, dairy foods are an important part of the diet. Therefore probiotic enriched products may be worth trying for those experiencing mild GI symptoms however, the results from this meta-analysis cannot be extrapolated to all probiotics since effects are known to be strain specific. It is also important to note that the evidence is not convincing for all of the different health benefits that are suggested to be conferred by probiotics and no health claims have been authorised by the European Food Safety Authority.

References

AtlanStat and Guyonnet, D. (2012) Study Report NU325: Effects of the Consumption of Fermented Dairy Product on Gastrointestinal Well-being in a Healthy Population of Women with Minor Digestive Symptoms:Final Version. Palaiseau: Danone Research, Centre Daniel Carasso.

De la Motte, S., Skoda, D., Coroller-Faivre, M., Elhiar, C. and Guyonnet, D. (2008) Study Report NU228: Effect of the consumption of a fermented dairy product on gastrointestinal well-being and health-related quality of life in a global population of women with minor digestive symptoms. Palaiseau: Danone Research, Centre Daniel Carasso.

Donazzolo, Y., Matuchansky, C., Pelletier, X., Guyonnet, D. and Perrin, C. (2007) Study Report NU200: Effect of the Consumption of a Fermented Dairy Product on Stool Frequency and Digestive Symptoms of Subjects with a Low Stool Frequency. Palaiseau: Danone Research, Centre Daniel Carasso.

Ford, A., Quigley, E., Lacy, B., Lembo, A., Saito, Y., Schiller, L. et al. (2014) Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol 109: 1547–1561.

Guyonnet, D., Schlumberger, A., Mhamdi, L., Jakob, S. and Chassany, O. (2009) Fermented milk containing Bifidobacterium lactis DN-173 010 improves gastrointestinal well-being and digestive symptoms in women reporting minor digestive symptoms: a randomised, double-blind, parallel, controlled study. Br J Nutr 102: 1654–1662.

Marteau, P., Guyonnet, D., Lafaye de Micheaux, P. and Gelu, S. (2013) A randomized, doubleblind, controlled study and pooled analysis of two identical trials of fermented milk containing probiotic Bifidobacterium lactis CNCM I-2494 in healthy women reporting minor digestive symptoms. Neurogastroenterol Motil 25: 331–e252.

Menees, Stacy B., et al. "The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis." The American journal of gastroenterology 107.1 (2012): 28-35.

Miller, Larry E., Angela K. Zimmermann, and Arthur C. Ouwehand. "Contemporary meta-analysis of short-term probiotic consumption on gastrointestinal transit." World journal of gastroenterology 22.21 (2016): 5122.

Tanguy, J., Picard, P. and Donazollo, Y. (2014) Statistical Report – Post-Hoc Analyses: Effect of the Consumption of a Fermented Dairy Product on Stool Frequency and Digestive Symptoms of Subjects with a Low Stool Frequency (NU200). Final Version. Palaiseau: Danone Research: Centre Daniel Carasso.