Effects of the food matrix on probiotic’s efficacy: how much should we care?

By Gabriel Vinderola PhD, Researcher at the Dairy Products Institute (National Scientific and Technical Research Council – CONICET) and Associate Professor at the Food Technology and Biotechnology Department, Faculty of Chemical Engineering, National University of Litoral, Santa Fe, Argentina.

The issue of to what extent food components may affect probiotic efficacy when compared to the strain delivered as supplement has lately been the subject of debate. This is especially so in the context of the Codex Alimentarius guidelines on probiotics, presently under development.

When considering the importance of the food formulation delivering the probiotic, it’s worthwhile to keep in mind that people may get their daily probiotic together with an enormous variety of foods. For instance, one person may get the probiotic at breakfast along with a yoghurt or with cereal, whereas another person may choose to consumer a fruit juice, while a third may get the probiotic dose before a meal consisting of pasta, meat and vegetables. In those cases, the same strain can undergo gastrointestinal passage in the context of very different food exposures. Does this suggest that perhaps the specific food format is not so critical? What does research tell us?

An interesting, however in vitro, study was conducted by Grześkowiak et al. (2011). In this work, Lactobacillus rhamnosus GG was recovered from more than 12 foods and supplements and its ability to inhibit food pathogens was assessed in vitro. Authors showed that even when the inhibitory capacity was quantitatively different among isolates, the qualitative probiotic capacity of inhibiting pathogens was present in all of them. That is to say, the probiotic capacity had been retained to a somewhat greater or lesser degree, regardless the matrix.

Few human studies have measured to what extent a health endpoint changes when a probiotic is delivered in different food matrixes. For instance, Saxelin et al. (2010) showed that the administration matrix (capsules, yogurt or cheese) did not influence the faecal quantity of lactobacilli, but affected faecal counts of propionibacteria and bifidobacteria. However no health endpoint was considered in this study. Several studies demonstrate that dairy products are able to confer enhanced protection during gastrointestinal transit in in vitro settings (Vinderola et al., 2000; Sagheddu et al., 2018; da Cruz Rodrigues et al., 2019), suggesting that dairy products may be better at delivering an efficacious dose of probiotic. But again, no clinical endpoint was measured in these studies.

The first comparative study on the probiotic capacity of a strain delivered in food or supplement was reported by Isolauri et al. (1991). Authors demonstrated that Lactobacillus GG either in fermented milk or freeze-dried powder was effective in shortening the course of acute diarrhea. Later on, Meng et al. (2016) found similar patterns of immune stimulation when studying the impact of Bifidobacterium animalis subsp. lactis BB12 administration in yoghurt or capsules on the upper respiratory tract of healthy adults.

As these kinds of studies are scarce, we can look to meta-analysis where the same strain is compared for the same clinical endpoint, but in studies conducted by different groups in different matrixes. For instance, Szajewska et al. (2013) concluded that Lactobacillus GG delivered in capsules or fermented milk significantly reduced the duration of diarrhea and Urbańska et al. (2016) reported that L. reuteri DSM 17938 delivered in either capsules or infant formula reduced the duration of diarrhoea and increased the chance of cure.

In vitro studies find that survival of the probiotic delivered in different food matrices through a (simulated) gastrointestinal transit may quantitatively differ, but no matrix completely eliminates probiotic capacity. Human clinical trials comparing different matrices with a clear health endpoint are scarce, but a general conclusion seems to emerge: regardless of the food matrix, the probiotic effect is achieved.  When the data are assessed through meta-analysis, the top of the “levels of evidence” in the pyramid of evidence-based studies, the probiotic capacity exists for the same strain among different studies, conducted by different research groups, using different food matrices.

In many countries regulators require that the probiotic effect be demonstrated in the same food or supplement that will be offered to consumers. This is a conservative approach in the lack of other evidence, but it may be challenging at the same time for probiotic food development, as any new food, even similar to one already existing, may require new human clinical studies to demonstrate efficacy. This approach may raise economic and ethical concerns too, and be discouraging for the future of probiotics.

Surely additional clinical trials directly comparing effects among different delivery matrices would provide clarity on the importance of this factor to probiotic functionality. Until that time, regulators should enable probiotic food manufacturers to offer a sound scientific rationale that bio-equivalency of different matrices could be expected, and thereby circumvent the requirement need to re-conduct human clinical trials on probiotics delivered in new matrices.

 

References

da Cruz Rodrigues VC, Salvino da Silva LG, Moreira Simabuco, F, Venema K, Costa Antunes AE. Survival, metabolic status and cellular morphology of probiotics in dairy products and dietary supplement after simulated digestion. J Funct. Foods, 2019, 55, 126-134.

Grześkowiak Ł, Isolauri E, Salminen S, Gueimonde M. Manufacturing process influences properties of probiotic bacteria. Br J Nutr. 2011, 105(6):887-94.

Isolauri E, Juntunen M, Rautanen T, Sillanaukee P, Koivula T. A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children.

Meng H, Lee Y, Ba Z, Peng J, Lin J, Boyer AS, Fleming JA, Furumoto EJ, Roberts RF, Kris-Etherton PM, Rogers CJ. Consumption of Bifidobacterium animalis subsp. lactis BB-12 impacts upper respiratory tract infection and the function of NK and T cells in healthy adults. Mol Nutr Food Res. 2016, 60(5):1161-71.

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Sagheddu V, Elli M, Biolchi C, Lucido J, Morelli L. Impact of mode of assumption and food matrix on probiotic viability. J Food Microbiol. 2018, 2.

Saxelin M, Lassig A, Karjalainen H, Tynkkynen S, Surakka A, Vapaatalo H, Järvenpää S, Korpela R, Mutanen M, Hatakka K. Persistence of probiotic strains in the gastrointestinal tract when administered as capsules, yoghurt, or cheese. Int J Food Microbiol. 2010, 144(2): 293-300.

Szajewska H, Skórka A, Ruszczyński M, Gieruszczak-Białek D. Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children-updated analysis of randomised controlled trials. Aliment Pharmacol Ther. 2013 Sep;38(5):467-76.

Urbańska M, Gieruszczak-Białek D, Szajewska H. Systematic review with meta-analysis: Lactobacillus reuteri DSM 17938 for diarrhoeal diseases in children. Aliment Pharmacol Ther. 2016, 43(10):1025-34.

Vinderola G, Prosello W, Ghiberto D, Reinheimer J. Viability of  probiotic- (Bifidobacterium, Lactobacillus acidophilus and Lactobacillus casei) and non probiotic microflora in Argentinian Fresco Cheese (2000). J Dairy Sci. 2000, 83 (9), 1905-1911.