The Development of High-Quality Multispecies Probiotic Formulations: From Bench to Market.

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. To date, there is an increasing number of commercially available products containing probiotics on the market. Probiotics have been recommended by health care professionals for reasons ranging from their long-term immunomodulatory effects to proven benefits in the management of different health conditions. For probiotic products, there are several important aspects that determine the success rate of the development from bench to market. The aim of this review is to explore how the current knowledge on microbe-microbe and host-microbe interactions can be used to develop high-quality, evidence-based probiotic formulations, specifically probiotic dietary supplements, with a focus on the selection of safe strains with relevant functional properties. In addition, we will highlight aspects of the probiotic manufacturing process that need to be considered during the product development and the subsequent manufacturing process to guarantee consistent efficacy of a probiotic product. For each high-quality probiotic formulation, it is important to screen multiple strains, and select only those strains that show relevant functional properties and that can be considered safe for human consumption. In addition, it is imperative that attention is paid to the product development and manufacturing process, and that safety and quality properties are monitored. Importantly, the beneficial effects of probiotics should be evaluated in product efficacy studies and post-marketing surveys in order to demonstrate their clinical efficacy. All these aspects need to be evaluated and validated during the development of a successful high-quality and ready-to-market probiotic.

Beneficial microbiota. Probiotics and pharmaceutical products in functional nutrition and medicine.

The article is mainly devoted to such representatives of gut microbiota as lactic acid bacteria and bifidobacteria, with minor accent on less frequently used or new probiotic microorganisms. Positive effects in treatment and prevention of diseases by different microbial groups, their metabolites and mechanisms of action, management and market of probiotic products are considered.

Expanding the reach of probiotics through social enterprises.

The rapid rise in microbiome and probiotic science has led to estimates of product creation and sales exceeding $50 billion within five years. However, many people do not have access to affordable products, and regulatory agencies have stifled progress. The objective of a discussion group at the 2017 meeting of the International Scientific Association for Probiotics and Prebiotics was to identify mechanisms to confer the benefits of probiotics to a larger portion of the world's population. Three initiatives, built around fermented food, were discussed with different methods of targeting populations that face enormous challenges of malnutrition, infectious disease, poverty and violent conflict. As new candidate probiotic strains emerge, and the market diversifies towards more personalised interventions, manufacturing processes will need to evolve. Information dissemination through scientific channels and social media is projected to provide consumers and healthcare providers with rapid access to clinical results, and to identify the nearest location of sites making new and affordable probiotic food and supplements. This rapid translation of science to individual well-being will not only expand the beneficiaries of probiotics, but also fuel new social enterprises and economic business models.

Effects of perioperative supplementation with pro-/synbiotics on clinical outcomes in surgical patients: A meta-analysis with trial sequential analysis of randomized controlled trials.

BACKGROUND & AIMS: The Potential benefits and possible risks of perioperative supplementation with probiotics/synbiotics in surgical patients are not fully understood. Recent evidence has rapidly evolved and conveys conflicting results. Thus, we undertook a meta-analysis of randomized controlled trials (RCTs) to valuate the effectiveness, safety, cost-effectiveness and quality of life of perioperative supplementation with pro-/synbiotics. METHODS: We systematically searched PubMed, Embase and the Cochrane Library through October 2015 to identify RCTs that assessed the effects of perioperative supplementation with pro-/synbiotics in surgical patients. The predefined primary efficacy outcome was surgical site infection (SSI). Random-effects model was applied to pool outcome data accounting for clinical heterogeneity. RESULTS: Our meta-analysis included data from 34 trials comprising 2634 participants, of whom 1300 received perioperative pro-/synbiotics intervention and 1334 received valid control treatment. Compared with the control group, patients in the pro-/synbiotics group had a lower risk of SSI (relative risk: 0.65; 95% confidence interval: 0.51, 0.84; P = 0.0007). Trial sequential analysis confirmed the evidence was sufficient and conclusive. Subgroup analyses indicated the findings were consistent in all subgroup analyses except for the probiotics, enteral feeding, pre-/postoperative and live transplantation subgroups. Pro-/synbiotics also reduced the incidence of other infectious complications (including any infection, pneumonia, urinary tract infection, wound infection and sepsis); shortened antibiotic therapy, intensive care unit stay and hospital stay; and promoted earlier first defecation and first bowel movement. Pro-/synbiotics further reduced the incidence of abdominal side effects, lowered hospital costs and improved the Gastro-Intestinal Quality of Life. CONCLUSIONS: For surgical patients, perioperative supplementation with pro-/synbiotics is effective in preventing or controlling SSI and other infectious complications. Perioperative pro-/synbiotics might also be associated with fewer side effects, lower hospital cost and better quality of life. Current evidence indicated that perioperative synbiotics supplementation is preferred and recommended as an adjunct in surgical patients.

Development and utility of the FDA 'GutProbe' DNA microarray for identification, genotyping and metagenomic analysis of commercially available probiotics.

AIM: Lactic acid bacteria are beneficial microbes added to many food products and dietary supplements for their purported health benefits. Proper identification of bacteria is important to assess safety as well as proper product labelling. A custom microarray (FDA GutProbe) was developed to verify accurate labelling in commercial dietary supplements. METHODS AND RESULTS: Strain-specific attribution was achieved with GutProbe array which contains genes from the most commonly found species in probiotic supplements and food ingredients. Applied utility of the array was assessed with direct from product DNA hybridization to determine (i) if identification of multiple strains in one sample can be conducted and (ii) if any lot-to-lot variations exist with eight probiotics found on the US market. CONCLUSIONS: GutProbe is a useful tool in identifying a mixture of microbials in probiotics and did reveal some product variations. In addition, the array is able to identify lot-to-lot differences in these products. These strain level attribution may be useful for routine monitoring of batch variation as part of a 'Good Manufacturing Practices' process. SIGNIFICANCE AND IMPACT OF THE STUDY: The FDA GutProbe is an efficient and reliable platform to identify the presence of microbial ingredients and determining microbe differences in dietary supplements. The GutProbe is a fast, rapid method for direct community profiling or food matrix sampling.

Nutraceuticals and botanicals: overview and perspectives.

The discovery, development and marketing of food supplements, nutraceuticals and related products are currently the fastest growing segments of the food industry. Functional foods can be considered part or borderline to these products and may be defined as foods or food ingredients that have additional health or physiological benefits over and above the normal nutritional value they provide. This trend is driven by several factors, mainly due to the current consumer perceptions: the first and dominant being 'Natural is good', and other secondary, such as the increasing cost of many pharmaceuticals and their negative secondary effects, the insistent marketing campaign, the increasing perception of the need of a healthy diet and its importance in the health and homeostasis organism conditions. However, the central point is that nutraceuticals, botanicals and other herbal remedies, including the entry of new functional foods, are important because of their acceptance as the novel and modern forms to benefit of natural substances. Due to the rapid expansion in this area, the development of several aspects is considered as it could influence the future of the market of these products negatively: an imbalance existing between the increasing number of claims and products on the one hand, the development of policies to regulate their application and safety on the other, rapid and valuable controls to check the composition, including the plant extracts or adulteration to improve efficacy, like the presence of synthetic drugs. It is interesting to see that, from the negative factors reported by the market analysts, a change in consumers preferences is absent. The functional properties of many plant extracts, in particular, are being investigated for potential use as novel nutraceuticals and functional foods. Although the availability of scientific data is rapidly improving, the central aspect concerns the validation of these products. The first step of this crucial aspect is the security of the composition, obtained by the useful and adapted analytical approach. On the other hand, in the first instance, security is assured by the millenary use as food of the great majority of these plants. The importance and the novelty of functional food are inherent in the possibility to renew the secure use of plants to maintain healthiness of man in novel forms of use adapted to modern times. The market of 'other substances', after the emergence of the first period of enthusiastic explosion, is entering into the maturation period, with three important arguments to face: (a) security in composition, production and sale, avoiding easy conversions or convenient approaches and favouring competence and professionalism, (b) definition of influence of metabolic aspects, including scientific validation and (c) regulatory aspects, e.g. the claims definition and relative influences. The last aspect seams to be in primis the most crucial and fundamental to the future of all the sectors. The role of European Food and Safety Authority (EFSA) in the EU market must be considered and consequences if negative decisions on 'other substances' claim will be adopted in each country's legislation.

Growth promotion of Bifidobacterium species by poultry bone and meat trimming hydrolyzate.

UNLABELLED: The growth of bifidobacteria that are employed in the production of functional food is often slow or limited, even on synthetic media. In this study, we investigated whether a peptide hydrolyzate (functional animal protein [FAP]), from poultry bones and meat trimmings, could be a potential source of growth stimulators. The bifidogenic activity of FAP on 18 strains of Bifidobacterium species was assessed via 2 different techniques: turbidimetric measurements and a direct count by fluorescence microscopy. Growth experiments were performed in B12 broth as the basal medium, B12 broth supplemented with N-acetylglucosamine, and B12 broth supplemented with FAP. FAP supplementation yielded the highest maximum optical density (OD) and count values. The use of the microscopic fluorescence counts allowed for better evaluation of the extent of growth and assessment of the viability of cells. FAP from poultry bones and meat trimmings has potential as a growth stimulator for different bifidobacteria of human origin. FAP is a promising ingredient for inclusion in industrial media that are used to culture probiotic strains, including bifidobacteria, because it supports growth very well and maintains cells at a high level of viability. PRACTICAL APPLICATION: Proteinaceous hydrolyzate can be considered a promising ingredient for industrial media that are used to culture probiotic strains, including bifidobacteria, because it improves bacterial growth and maintains cells at a high level of viability.

Prevention of flu episodes with colostrum and Bifivir compared with vaccination: an epidemiological, registry study.

The aim of this study was to evaluate the efficacy of colostrum (ARD Colostrum) in association with the immunomodulator Bifivir in the prevention of flu episodes compared with anti-flu vaccination. The registry groups included no prevention, vaccination, vaccination+immunomodulators, and immunomodulators only. Groups were comparable for age and sex distribution. In the group without prevention there were 8 major episodes and 12 minor episodes out of 34 subjects (8-12/34); in the vaccination group the respective figures were 8-13/38; in the group treated with a combination of vaccination and immunomodulators (ARD Colostrum + Bifivir) the figures were 4-9/33; and in the group treated with immunomodulators only there were 11 viral episodes (3-8) in 36 subjects. The episodes in the vaccination+immunomodulators and immunomodulators only groups were significantly lower compared with the other two groups (P<0.05). The number of episodes registered with the immunnomodulators was significantly lower than those observed in patients using vaccination or no prevention (P<0.05). The number of days of disease was higher in untreated controls compared to the groups treated with immunomodulators (P<0.05) and 2 times higher in the vaccination group compared to the same groups (P<0.05). The average relative costs were significantly lower (2.3 times) in the immunomodulators groups in comparison with the other groups (P<0.05). No problems concerning tolerability or side effects were observed during the study. Compliance was very good. In conclusion, the administration of immunomodulators is very cost effective and appears to be more effective than vaccination to prevent flu.

Probiotic formulations and applications, the current probiotics market, and changes in the marketplace: a European perspective.

Europe is a multicultural continent where the consumption of fermented milks has traditionally been high in several countries. Thus, it is no wonder that the market for fermented dairy products with probiotic bacteria has been successful. The market for food applications of probiotics is clearly larger than that for probiotics sold in capsules, sachets, and other pharmaceutical forms. Yogurt-type drinks are the fastest-growing product category, but the diversity of probiotic food applications is not limited to milk-based products. Probiotic fruit juices, berry soups, and soy- and cereal-based fermented products are also sold. Some probiotic strains that are successful in Europe are marketed globally, but there is also a variety of local probiotic strains that are key players in their limited markets. The health messages of probiotic products have focused mainly on general well-being and support of gastrointestinal microbiota. However, because of newly accepted regulation from the European Union regarding health claims, such claims will be evaluated officially, which may substantially change their content. However, more-specific product claims may also appear on the market. This article describes trends and phenomena in mainly the food sector, which covers the most-successful probiotic applications, but food supplements are also discussed.

Probiotics--the friendly bacteria with market potential in global market.

With the growing interest in self-care and integrative medicine coupled with our health-embracing increasing population, recognition of the link between diet and health has never been stronger. As a result, the market for functional foods, or foods that promote health beyond providing basic nutrition, is flourishing. Within the functional foods movement is the small but rapidly expanding arena of probiotics - live microbial food supplements that beneficially affect an individual by improving intestinal microbial balance. The consumers' overwhelming interest in and demand for functional foods, including probiotics, make it imperative that health professionals stay abreast of the latest research findings and available products. The global market for functional foods in the coming years is predicted to grow rapidly. Although Japan currently accounts for about one-half of this market, the fastest rate of growth is expected to be in the United States. Probiotic products represent a strong growth area within the functional foods group and intense research efforts are under way to develop dairy products into which probiotic organisms such as Lactobacillus and Bifidobacterium species are incorporated. Such probiotic foods may modulate gut microbial composition, thereby leading to improved gut health, for example, through improved tolerance to lactose in lactose-intolerant individuals or improved resistance to pathogenic bacteria. The fast-growing probiotics market holds a wealth of opportunities, especially for those companies that understand and cater for the final consumer. This monograph provides a summary of research on the health benefits of probiotics and offers information regarding the global market potential of probiotics.

Performance and condemnation rate analysis of commercial turkey flocks treated with a Lactobacillus spp.-based probiotic.

The use of defined probiotic cultures in the poultry industry has recently become more common. However, few conclusive studies regarding their efficacy under commercial conditions have been reported in the scientific literature. We conducted a study that included 118 commercial turkey hen lots, ranging from 1,542 to 30,390 hens per lot, of either Nicholas or Hybrid genetic lines, to look at the effect of a selected commercial Lactobacillus-based probiotic (FM-B11) on turkey BW, performance, and health. Sixty lots received the probiotic, whereas 58 lots were controls without probiotic. The probiotic was administered for 3 consecutive days at placement (day of age) and at move-out (around 6 wk of age, movement from brooder to grower houses). The parameters collected, calculated, and analyzed (significance level P < 0.05) were market BW, average daily weight gain, feed conversion ratio, and cost of production. There was no interaction effect between the genetic line and probiotic effect. Therefore, data from the 2 genetic lines were combined for the statistical analysis of the probiotic effect. The probiotic significantly improved market BW and average daily gain by 190 and 1.63 g, respectively. The feed conversion ratio was not statistically different between treatments (2.176 vs. 2.192 for the probiotic and control, respectively). However, the cost of production was lower in the probiotic-treated (58.37 cents/kg of live turkey) than in the control (59.90 cents/kg of live turkey) lots. Condemnation rates were not significantly different between lots. When each premise was compared by level of performance as good, fair, or poor (grouping based on historical analysis of 5 previous flocks), the probiotic appeared to increase the performance of the poor and fair farms. Use of the selected commercial probiotic resulted in increased market BW and reduced cost of production.