Best practices for designing better clinical trials of probiotics and prebiotics

When considering of the intestine microbiome as a forest, the earlier situations of the land (intestine microbiome) might have an effect on how fertilizer (prebiotics) is distributed within the area and the quantity and number of vegetation, crops, and bushes (probiotics) that can develop. Nonetheless, though it appears biologically believable that an individual’s background weight-reduction plan might have an effect on the efficacy of microbiome-based interventions, just a few human research have investigated how the microbiome and host physiology reply to prebiotics and probiotics fluctuate and are influenced by background dietary consumption.

Writing in Nature Microbiology, a gaggle of scientists in vitamin, meals science, microbiology, and prebiotics and probiotics medical trials examines the influence of weight-reduction plan on how the microbiome and host reply to taking a prebiotic or probiotic.

Background weight-reduction plan can have an effect on responses to prebiotics. A randomized, double-blind, placebo-controlled crossover trial confirmed that agave inulin supplementation was more than likely to extend fecal Bifidobacterium and butyrate ranges in wholesome adults with the next dietary fiber consumption of their routine weight-reduction plan. Comparable findings have been noticed when exploring the influence of weight-reduction plan on satiety after supplementing with inulin. A randomized, double-blind, placebo-controlled crossover trial found that modifications in satiety after supplementation with 16 g/day of inulin for 3 weeks have been noticed in wholesome volunteers with greater fiber consumption at baseline (common dietary fiber consumption of 38.6 g/day) in comparison with these with a decrease fiber consumption (common dietary fiber consumption of 18 g/day). These knowledge recommend that routine high-fiber diets are related to a intestine microbiome extra conscious of a prebiotic.

Relating to probiotics, just one double-blind and placebo-controlled trial has explored the intestine microbiome and host response to a probiotic. Whereas there have been no modifications in metabolic syndrome markers in response to the probiotic, the authors reported important enhancements in triglycerides and diastolic blood strain in a subset of probiotic arm contributors who had a definite microbiome profile (enriched in Lachnospira and Eggerthella) on the finish of the research relative to the non-responders. The authors mentioned that greater intakes of whole sugars, added sugars, lactose, and a few micronutrients might drive diet-probiotic interactions that affected medical response to the probiotic.

Research displaying that synbiotics have better therapeutic efficacy than both probiotic or prebiotic parts administered alone additionally support that dietary elements might improve the efficacy of probiotics and prebiotics. Nonetheless, most synbiotics out there commercially are mixtures during which every probiotic(s) and prebiotic(s) work independently to realize a well being profit, and extra strong medical trials are wanted on synergistic synbiotics with their parts working collectively to result in ensuing well being profit(s).

The findings that response to probiotic and prebiotic dietary supplements could also be diet-dependent have been the seed for a workshop convened by the Worldwide Scientific Affiliation for Probiotics and Prebiotics, which resulted in ten suggestions to information the design and conduct of trials of prebiotics and probiotics:

1. Contemplate whether or not and methods to harmonize the weight-reduction plan of the research inhabitants earlier than intervention through the use of totally different levels of researcher intervention
2. Contributors shouldn’t be concerned in non secular festivals or holidays if their dietary consumption is altered
3. The composition of prebiotic or probiotic, and of the supply matrix, the supply, the dose/viable cell numbers per dose of the energetic ingredient, and the producer ought to be reported, contemplating that these variables can have an effect on prebiotic and probiotic effectiveness
4. Particulars of prebiotic or probiotic consumption (variety of doses, timing, meals) ought to be reported, in addition to contributors’ adherence to the therapy
5. Applicable microbiome analyses ought to be carried out to precisely interpret the position of background weight-reduction plan versus intervention-specific modifications
6. Dietary evaluation ought to be carried out at baseline and finish of intervention in human intervention research the place weight-reduction plan is one inclusion or exclusion criterion
7. Dietary evaluation ought to file microbiome-relevant weight-reduction plan exposures, together with fermented meals and postbiotics, though present meals databases don’t embrace related meals info that may have an effect on the microbiome (meals components, cooking strategies, and polyphenols, amongst others)
8. Dietary evaluation ought to embrace detailed info on vitamins, meals, meals teams, or dietary patterns, so long as they will have an effect on probiotics and prebiotics effectiveness
9. The strategy (meals information, 24h recall, or meals frequency questionnaire) and length of weight-reduction plan evaluation ought to rely on the analysis query and publicity of curiosity
10. A dietitian or nutritionist with analysis experience ought to be on the group, and shall be concerned not solely within the research design but in addition in accompanying the contributors, and dietary evaluation instruments and knowledge analyses

To sum up, weight-reduction plan is likely one of the most related elements influencing the human intestine microbiome, and it is usually time to contemplate it as a variable, along with gut physiology (e.g., transit time and pH), that may have an effect on how the microbiome and host reply to microbiome-targeted interventions.

References:

Whelan Okay, Alexander M, Gaiani C, et al. Design and reporting of prebiotic and probiotic clinical trials in the context of diet and the gut microbiome. Nat Microbiol. 2024; 9(11):2785-2794. doi: 10.1038/s41564-024-01831-6.

Holscher HD, Bauer LL, Gourineni V, et al. Agave inulin supplementation affects the fecal microbiota of healthy adults participating in a randomized, double-blind, placebo-controlled, crossover trial. J Nutr. 2015; 145(9):2025-2032. doi: 10.3945/jn.115.217331.

Healey G, Murphy R, Butts C, et al. Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study. Br J Nutr. 2018; 119(2):176-189. doi: 10.1017/S0007114517003440.

Wastyk HC, Perelman D, Topf M, et al. Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet. Intestine Microbes. 2023; 15(1):2178794. doi: 10.1080/19490976.2023.2178794.

De Giani A, Sandionigi A, Zampolli J, et al. Effects of inulin-based prebiotics alone or in combination with probiotics on human gut microbiota and markers of immune system: a randomized, double-blind, placebo-controlled study in healthy subjects. Microorganisms. 2022; 10(6):1256. doi: 10.3390/microorganisms10061256.

Procházková N, Laursen MF, La Barbera G, et al. Gut physiology and environment explain variations in human gut microbiome composition and metabolism. Nat Microbiol. 2024; 9:3210-3225. doi: 10.1038/s41564-024-01856-x.