Preclinical relevance of probiotics in type 2 diabetes: A systematic review

Abstract

Type 2 diabetes (T2DM) is among the most prevalent metabolic diseases in the world and may result in several long-term complications. The crosstalk between gut microbiota and host metabolism is closely related to T2DM. Currently, fragmented data hamper defining the relationship between probiotics and T2DM. This systematic review aimed at investigating the effects of probiotics on T2DM in animal models. We systematically reviewed preclinical evidences using PubMed/MEDLINE and Scopus databases, recovering 24 original articles published until September 27th, 2019. This systematic review was performed according to PRISMA guidelines. We included experimental studies with animal models reporting the effects of probiotics on T2DM. Studies were sorted by characteristics of publications, animal models, performed analyses, probiotic used and interventions. Bias analysis and methodological quality assessments were examined through the SYRCLE's Risk of Bias tool. Probiotics improved T2DM in 96% of the studies. Most studies (96%) used Lactobacillus strains, and all of them led to improved glycaemia. All studies used rodents as models, and male animals were preferred over females. Results suggest that probiotics have a beneficial effect in T2DM animals and could be used as a supporting alternative in the disease treatment. Considering a detailed evaluation of the reporting and methodological quality, the current preclinical evidence is at high risk of bias. We hope that our critical analysis will be useful in mitigating the sources of bias in further studies.

Keywords: animal model; diabetes mellitus; glycaemia; microbiota; nutrition; probiotic.

FIGURE 1

Flow diagram of the systematic review literature search results. Based on ‘Preferred Reporting Items for Systematic Reviews and Meta‐Analyses: The PRISMA Statement’. http://www.prisma‐statement.org. From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) ¹¹

FIGURE 2

Results of the risk of bias and methodological quality indicators for all included studies in this systematic review that evaluated the effect of probiotic treatment in T2DM. The items in the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). Risk of Bias assessment were scored with ‘yes’ indicating low risk of bias, ‘no’ indicating high risk of bias, or ‘unclear’ indicating that the item was not reported, resulting in an unknown risk of bias. Consider selection bias: was the allocation sequence adequately generated and applied? Were the groups similar at baseline or were they adjusted for confounders in the analysis? Was the allocation to the different groups adequately concealed? Consider performance bias: were the animals randomly housed during the experiment? Were the caregivers and/or investigators blinded from knowledge which intervention each animal received during the experiment? Were animals selected at random for outcome assessment? Consider detection bias: was the outcome assessor blinded? Consider attrition bias: were incomplete outcome data adequately addressed? Consider reporting bias: are reports of the study free of selective outcome reporting? Consider other biases: was the study apparently free of other problems that could result in high risk of bias? Consider overall quality: was it stated that the experiment was randomized at any level? Was it stated that the experiment was blinded at any level? % represent the percentage of the studies that are fulfilled the requirements for ‘Low risk of bias’ and ‘Unclear risk of bias’ and ‘High risk of bias’

FIGURE 3

Risk of bias summary shows studies' quality assessment at an individual level. (+) Low risk of bias. (−) High risk of bias. (?) Unclear risk of bias

FIGURE 4

Analysis of methodological bias (reporting quality) stratified by domains for each study included in the review. Dotted line indicates the mean quality score (%)

FIGURE 5

Summary of the main findings on the effects of probiotic use in animals with T2DM. CAT, catalase; G‐6‐Pase, glucose 6‐phosphatase; GLP‐1, glucagon‐like peptide‐1; PEPCK, phosphoenolpyruvate carboxykinase; PYY, peptide YY; ROS, reactive oxygen species; SCFAs, short‐chain fatty acids; SOD, superoxide dismutase