When thinking of the gut microbiome as a forest, the previous conditions of the land (gut microbiome) may affect how fertilizer (prebiotics) is distributed in the field and the amount and variety of vegetation, plants, and trees (probiotics) that will grow. However, although it seems biologically plausible that a person’s background diet may affect the efficacy of microbiome-based interventions, only a few human studies have investigated how the microbiome and host physiology respond to prebiotics and probiotics vary and are influenced by background dietary intake.

Writing in Nature Microbiology, a group of scientists in nutrition, food science, microbiology, and prebiotics and probiotics clinical trials examines the impact of diet on how the microbiome and host respond to taking a prebiotic or probiotic.

Background diet can affect responses to prebiotics. A randomized, double-blind, placebo-controlled crossover trial showed that agave inulin supplementation was most likely to increase fecal Bifidobacterium and butyrate levels in healthy adults with a higher dietary fiber intake in their habitual diet. Similar findings were observed when exploring the impact of diet on satiety after supplementing with inulin. A randomized, double-blind, placebo-controlled crossover trial found that changes in satiety after supplementation with 16 g/day of inulin for 3 weeks were observed in healthy volunteers with higher fiber intake at baseline (average dietary fiber intake of 38.6 g/day) compared to those with a lower fiber intake (average dietary fiber intake of 18 g/day). These data suggest that habitual high-fiber diets are associated with a gut microbiome more responsive to a prebiotic.

Regarding probiotics, only one double-blind and placebo-controlled trial has explored the gut microbiome and host response to a probiotic. While there were no changes in metabolic syndrome markers in response to the probiotic, the authors reported significant improvements in triglycerides and diastolic blood pressure in a subset of probiotic arm participants who had a distinct microbiome profile (enriched in Lachnospira and Eggerthella) at the end of the study relative to the non-responders. The authors discussed that higher intakes of total sugars, added sugars, lactose, and some micronutrients could drive diet-probiotic interactions that affected clinical response to the probiotic.

Studies showing that synbiotics have greater therapeutic efficacy than either probiotic or prebiotic components administered alone also support that dietary factors may enhance the efficacy of probiotics and prebiotics. However, most synbiotics available commercially are mixtures in which each probiotic(s) and prebiotic(s) work independently to achieve a health benefit, and more robust clinical trials are needed on synergistic synbiotics with their components working together to bring about resulting health benefit(s).

The findings that response to probiotic and prebiotic supplements may be diet-dependent were the seed for a workshop convened by the International Scientific Association for Probiotics and Prebiotics, which resulted in ten recommendations to guide the design and conduct of trials of prebiotics and probiotics:

  1. Consider whether and how to harmonize the diet of the study population before intervention by using different degrees of researcher intervention
  2. Participants should not be involved in religious festivals or holidays if their dietary intake is altered
  3. The composition of prebiotic or probiotic, and of the delivery matrix, the source, the dose/viable cell numbers per dose of the active ingredient, and the manufacturer should be reported, considering that these variables can affect prebiotic and probiotic effectiveness
  4. Details of prebiotic or probiotic intake (number of doses, timing, meals) should be reported, as well as participants’ adherence to the treatment
  5. Appropriate microbiome analyses should be performed to accurately interpret the role of background diet versus intervention-specific changes
  6. Dietary assessment should be performed at baseline and end of intervention in human intervention studies where diet is one inclusion or exclusion criterion
  7. Dietary assessment should record microbiome-relevant diet exposures, including fermented foods and postbiotics, although current food databases do not include relevant food information that can affect the microbiome (food additives, cooking methods, and polyphenols, among others)
  8. Dietary assessment should include detailed information on nutrients, food, food groups, or dietary patterns, as long as they can affect probiotics and prebiotics effectiveness
  9. The method (food records, 24h recall, or food frequency questionnaire) and duration of diet assessment should depend on the research question and exposure of interest
  10. A dietitian or nutritionist with research expertise should be on the team, and will be involved not only in the study design but also in accompanying the participants, and dietary assessment tools and data analyses

 

To sum up, diet is one of the most relevant factors influencing the human gut microbiome, and it is also time to consider it as a variable, together with gut physiology (e.g., transit time and pH), that can affect how the microbiome and host respond to microbiome-targeted interventions.

 

References:

Whelan K, 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. Gut 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.