Maneerat, S. et al. Consumption of Bifidobacterium lactis Bi-07 by healthy elderly adults enhances phagocytic activity of monocytes and granulocytes. J. Nutr. Sci. 2, e44 (2013).

Islek, A., Sayar, E., Yilmaz, A. & Artan, R. Bifidobacterium lactis B94 plus inulin for Treatment of Helicobacter pylori infection in children: does it increase eradication rate and patient compliance? Acta Gastroenterol. Belg. 78, 282–286 (2015). Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concepts of prebiotics. J Nutr 1995;125(6):1401-1412.As for probiotics, prebiotics and synbiotics, it might be possible a priori to stratify study participants to enhance either the magnitude of the response or the number of responders to a given synbiotic treatment. The baseline composition of gut microbiota of study participants could be one useful stratification factor 91, 92. This stratification might improve mechanistic understanding of observed effects and could be useful for characterizing responders and non-responders. Ultimately, this approach could enable better translation of clinical trial outcomes to those who are likely to benefit. Martin, R. & Langella, P. Emerging health concepts in the probiotics field: streamlining the definitions. Front. Microbiol. 10, 1047 (2019). As with probiotics, the desired outcome after giving prebiotics is improvement of host health. 21 However, the specific aim of giving prebiotics is to promote growth and function of the beneficial bacteria already present in the gut. Intake of prebiotics can significantly modulate the colonic microbiota by increasing the number of specific bacteria and thus changing the composition of the microbiota. 23 Prebiotics are metabolized by the resident microbiota of the colon, which, depending on fermentability, will result in the production of the short-chain fatty acids butyrate, propionate, and acetate. 23 These metabolites will diffuse through gut enterocytes and provide either local effects (e.g., enhance the intestinal epithelial barrier, decrease pro-inflammatory cytokines, regulate intestinal motility) or systemic effects (e.g., provide energy for the host). 24,25 Apart from direct prebiotic effects, dietary fibers can have additional functions in the GI tract. Psyllium, for example, has water-binding and bile acid–binding properties that improve fecal consistency, increase the intestinal mucus layer, and have beneficial effects on cell proliferation in the intestinal tract. 26 Synbiotics ISAPP is a non-profit collaboration of scientists dedicated to advancing scientific excellence and providing objective, science-based information on probiotics and prebiotics. The organization’s activities are funded by companies involved in the sale of probiotics and prebiotics, but ISAPP is guided by an international, all-volunteer academic board that functions independently. This ISAPP-organized panel was composed of experts in microbiology, nutrition and gastrointestinal physiology, including many who were involved in the latest updates of the probiotic 12 and prebiotic 13 definitions according to ISAPP. Panellists were charged with accomplishing the following goals: consider what a synbiotic is and provide a clear, concise and testable definition; suggest the appropriate experimental conditions necessary to establish synbiotic activity; describe the evidence required to demonstrate the health benefits and establish safety; and provide guidance for stakeholders, including researchers, industry, public health professionals and regulatory agencies.

Hadi, A., Alizadeh, K., Hajianfar, H., Mohammadi, H. & Miraghajani, M. Efficacy of synbiotic supplementation in obesity treatment: a systematic review and meta-analysis of clinical trials. Crit. Rev. Food Sci. Nutr. 60, 584–596 (2020). White R, Atherly T, Guard B, et al. Randomized, controlled trial evaluating the effect of multi-strain probiotic on the mucosal microbiota in canine idiopathic inflammatory bowel disease. Gut Microbes 2017;8(5):451-466.David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014). Beneficial effect(s) of a synbiotic on health must be confirmed in the target host, which might include humans, companion animals, or agricultural species or a subpopulation (such as different age or developmental stage, health status, sex or living situation) thereof. Can dogs be used as a model for studying human disease? We have a collaboration with pediatric oncologists evaluating if canine sarcoma can be used as a model for pediatric human sarcoma.

Pisano, A., D’Arrigo, G., Coppolino, G. & Bolignano, D. Biotic supplements for renal patients: a systematic review and meta-analysis. Nutrients 10, 1224 (2018).

Porras-Dominguez, J. R. et al. Frucooligosaccharides purification: complexing simple sugars with phenylboronic acid. Food Chem. 285, 204–212 (2019). A prebiotic, consisting of fructo-oligosaccharide (FOS) and acacia (Gum arabic), to feed and stimulate the growth of beneficial bacteria.

Sanders, M. E. et al. Effects of genetic, processing, or product formulation changes on efficacy and safety of probiotics. Ann. NY Acad. Sci. 1309, 1–18 (2014). Nixon SL, Rose L, Muller AT. Efficacy of an orally administered anti-diarrheal probiotic paste (Pro-Kolin Advanced) in dogs with acute diarrhea: a randomized, placebo-controlled, double-blinded clinical study. J Vet Intern Med 2019;33(3):1286-1294.

Symbiotic 180-S's unique formulation contains 9 strains of beneficial bacteria, with natural prebiotic (chicory root extract) and digestive enzymes. Reddy, B. S. et al. Randomized clinical trial of effect of synbiotics, neomycin and mechanical bowel preparation on intestinal barrier function in patients undergoing colectomy. Br. J. Surg. 94, 546–554 (2007). The business community plays a vital part in translating the outcomes of fundamental and clinical research into commercial products that can benefit consumers. To the extent that industry funds research, it is essential that studies adhere to well-established guidelines to manage conflicts of interest and minimize bias 94, 95. Further, industry bears the duty of responsible manufacture, quality control and marketing of synbiotic products. It is incumbent on industry to follow good manufacturing practices, engage in truthful labelling and product promotion as well as adhere to appropriate use of the term ‘synbiotics’. Media