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Protexin Veterinary Synbiotic D-C Daily probiotic and prebiotic capsules for dogs and cats (Pack of 1, 50 Capsules)

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Closa-Monasterolo, R. et al. Safety and efficacy of inulin and oligofructose supplementation in infant formula: results from a randomized clinical trial. Clin. Nutr. 32, 918–927 (2013). There are multiple ways to design a synbiotic trial intended to examine health effects in the target host. Here, we provide some recommendations based on the criteria established herein to demonstrate complementary or synergistic synbiotics. Pre-specified subgroup analyses should be considered based on the relevant clinical factors (such as sex and age), baseline gut microbiota factors, dietary factors (such as typical dietary fibre intake) or other relevant factors (such as responder analysis). The number of experimental groups or ‘study arms’ required to prove efficacy and support mechanistic understanding will depend on the existing level of evidence for the component live microorganism(s) and selectively utilized substrate(s) as well as the researchers’ intent to determine whether components of the test mixture are complementary or acting as synergistic synbiotics (Table 2). Pham, V. T. & Mohajeri, M. H. The application of in vitro human intestinal models on the screening and development of pre- and probiotics. Benef. Microbes 9, 725–742 (2018). 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.

The EU-registered probiotic Enterococcus faecium (DSM 10663/ NCIMB 10415) 4b1707, to help repopulate the intestine with beneficial micro-organisms. Sirvan, B. N., Usta, M. K., Kizilkan, N. U. & Urganci, N. Are synbiotics added to the standard therapy to eradicate Helicobacter pylori in children beneficial? A randomized controlled study. Euroasian J. Hepatogastroenterol. 7, 17–22 (2017).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). Government of Canada. Accepted Claims about the Nature of Probiotic Microorganisms in Food https://www.canada.ca/en/health-canada/services/food-nutrition/food-labelling/health-claims/accepted-claims-about-nature-probiotic-microorganisms-food.html (2009). A two-arm parallel or crossover study would be sufficient to test a complementary synbiotic. The aim is to demonstrate that the combination is better than the placebo group with a relevant health end point. As a demonstrated prebiotic is used to formulate a complementary synbiotic, we do not require that selective utilization by the indigenous microbiota be reconfirmed in this clinical trial. Measurement of selective utilization Gerasimov, S. V., Vasjuta, V. V., Myhovych, O. O. & Bondarchuk, L. I. Probiotic supplement reduces atopic dermatitis in preschool children: a randomized, double-blind, placebo-controlled, clinical trial. Am. J. Clin. Dermatol. 11, 351–361 (2010). D’Angelo, S., Fracassi, F., Bresciani, F., Galuppi, R., Diana, A., Linta, N., Bettini, G., Morini, M., Pietra, M., 2018. Effect of Saccharomyces boulardii in dogs with chronic enteropathies: double-blinded, placebo-controlled study. Veterinary Record.. doi:10.1136/vr.104241

Liu, L., Li, P., Liu, Y. & Zhang, Y. Efficacy of probiotics and synbiotics in patients with nonalcoholic fatty liver disease: a meta-analysis. Dig. Dis. Sci. 64, 3402–3412 (2019). This meta-analysis highlights the benefits of synbiotics for the hallmarks of non-alcoholic fatty liver disease, liver steatosis, liver enzymes, lipid profiles and liver stiffness.Across studies, species from the genera Lactobacillus, Bifidobacterium and Streptococcus are the most commonly used live microorganisms within the formulations tested. The substrate components are usually galacto-oligosaccharides, inulin or fructo-oligosaccharides but doses vary considerably, from as low as 100 mg to as much as 10–15 g per day. For example, in a double-blind RCT, twice daily consumption of a synbiotic composed of Lactobacillus acidophilus 10 (10 9 CFU), Lactobacillus rhamnosus HS111 (10 9 CFU), Lactobacillus casei 10 (10 9 CFU), Bifidobacterium bifidum (10 9 CFU) and fructo-oligosaccharides (100 mg) 4 days before and 10 days after surgery for periampullary neoplasms resulted in a lower number of postoperative infections, a shorter duration of antibiotic therapy, fewer non-infectious complications, shorter length of hospital stay and reduced mortality than in patients receiving a placebo (sucrose) 45. Although such low doses would not be expected to provide a prebiotic effect in complementary synbiotics, they could, in theory, be sufficient to stimulate a cognate microorganism in a synergistic synbiotic formulation. In one RCT 46 of 225 adults with overweight and obesity, a combination of Bifidobacterium animalis subsp. lactis 420 and polydextrose (12 g per day) resulted in a relative reduction in body fat mass of 4.5%, whereas the individual treatments had no effect. However, selective utilization was not established in this study. Thus, by itself, this study does not provide sufficient evidence that the tested combination was either a complementary or a synergistic synbiotic. Does treatment of dysbiosis improve outcomes in cancer patients and in patients with other diseases? Probiotics: (180 million CFU/g) Lactobacillus acidophilus, L.casei, L. salivarius, L.plantarum, L.rhamnosus, L.brevis, Bifidobacterium bifidum, B.lactis, S. thermophilus.

Generating this evidence requires appropriately designed, adequately powered experimental trials conducted on the target host. These studies should follow standard human trial design and reporting guidelines 48 and consider best practices for diet–microbiota research 49. The study should also meet the criteria outlined in CONSORT 48 and should be registered, including a description of all outcomes, prior to recruitment. These CONSORT criteria include guiding principles for microorganisms, microbiota-related compliance and outcome measures, relevant subgroups, and statistical considerations for evaluating the microbiota as a mediator of clinical effects. Chang, Y. S. et al. Synbiotics for prevention and treatment of a dermatitis: a meta-analysis of randomized clinical trials. JAMA Pediatr. 170, 236–242 (2016). This meta-analysis provides evidence that supports the use of synbiotics for the treatment of atopic dermatitis, which is thought to be associated with altered gut microbiota that promote an environment that is more susceptible to allergic disease. Sanders, M. E. et al. Safety assessment of probiotics for human use. Gut Microbes 1, 164–185 (2010). Barry KA, Middelbos IS, Vester Boler BM, et al. Effects of dietary fiber on the feline gastrointestinal metagenome. J Proteome Res 2012;11(12):5924-5933. Aktas MS, Ozkanlar Y. Efficacy of Saccharomyces boulardii as a probiotic in dogs with lincomycin induced diarrhoea. Bull Vet Inst Pulawy 2007;51(3):365-369.Probiotics are beneficial bacteria that can help to re-establish the normal microbiota. They are particularly effective when delivered together with a prebiotic, a source of nutrition that stimulates growth. A synbiotic can be applied to intestinal or extra-intestinal microbial ecosystems and might be formulated into products fitting an array of regulatory categories (such as foods, non-foods, feeds, drugs or nutritional supplements). Mofidi, F. et al. Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial. Br. J. Nutr. 117, 662–668 (2017).

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