Dr Satyanarayana Kandukuri, Food Processing Practice Lead, Sathguru Management Consultants
Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host”. Live microorganisms may be present in many foods and supplements, but only characterised strains with a scientifically demonstrated effect on health should be called probiotics. The criteria for probiotics include documented health benefit, microbes being alive at the time of consumption, microbes at dosage/levels that provide benefit, microbes taxonomically defined to strain level, availability of genome sequence of microbes and safety for intended use. In the past few years, the probiotics market has gained momentum in the functional foods category as well as supplements category.
The drivers for onward momentum in the probiotics industry come from – increasing scientific studies and documentation of various health benefits of probiotics, increasing consumer awareness and understanding of the role of probiotics in health, improved formulations and stabilisation technologies expanding the applications of probiotics to non-dairy and non-refrigerated food categories.
The key requirements for probiotics products to be successful in the market include – number of colonies forming units (CFUs) reaching the gut, stability in the gut, efficacy for intended benefit, stability on the shelf, stability in the food matrix, as well as processing conditions and delivery methods/ controlled release at the site of action. The critical success factors in probiotics are: (i) strain development, (ii) clinical studies & (iii) product development. These critical areas are currently witnessing wide interest and new developments by industry players.
Strain Development
Bacterial strains like several species of Lactobacillus, Bifidobacterium and non-bacterial strains of Saccharomyces boulardii and S. cerevisiae are commonly used in the food industry. The probiotic organisms were mainly sourced from the gut or from traditional fermented foods and hence majority of the probiotics used in commercial products were limited to the narrow genera including Lactobacillus and Bifidobacterium. The popularity of the strains/ species belonging to Lactobacillus and Bifidobacterium was also due to their Generally Regarded as Safe (GRAS) status in USA or granted status of Qualified Presumption of Safety (QPS) by the European Food Safety Authority (EFSA). Several commercial players used rigorous strain selection criteria to screen natural strains with the desired properties, stability and stress-adaptation. In recent years, spore forming bacteria like Bacillus coagulans are witnessing a rapid growth and adoption due to better stability and survival in foods with extreme processing conditions like pH, heat, cold, and pressure. The use of stable Bacillus coagulans has resulted in expansion of the category of probiotic products by food formulators as well as use in ambient temperature storage, in contrast to the Lactobacillus and Bifidobacterium which were commonly used in refrigerated (dairy) or frozen products.
The developments and significant cost reductions in genome sequencing and improved culturing methodologies are providing opportunities to isolate and characterise a new range of microorganisms from human microbiomes. Some of the bacteria that have been isolated from the human gut with probiotic potential include Akkermansia muciniphila, Bacteroides spp., Eubacterium spp., Faecalibacterium prausnitzii and Roseburia intestinalis. These species offer physiological benefits such as the production of propionates, butyrates, and other biomolecules, which are not always directly provided by traditional probiotic strains. However, the novel genera and species that have no history of use would require elaborate safety assessments, and the commercialisation path may require submissions/ regulatory approvals under GRAS, QPS, or emerging regulatory frameworks such as live biotherapeutic products category by USFDA. Moreover, new sets of microorganisms can pose challenges in terms of production processes like requirement of rich growth media and strict anaerobic conditions. Of the novel genera under research, significant work has been done on A. muciniphila including preclinical animal testing, human safety assessment, stability and efficacy testing in improving several metabolic parameters.
In addition to the human gut microbiome, other microbial niches being explored for isolation of novel species and as targets for intervention include oral cavity, skin, urinary tract etc. Fermented and unfermented foods continue to be a source for future probiotic development.
Clinical Studies
Human clinical trials are crucial for probiotics development and to ensure science-based claims. In addition to the widely known beneficial effects on gut and immune health, new evidence is emerging on other indications like inflammatory bowel disease, oral health, skin health, mood and cognition, obesity and metabolic diseases. A recent study, commissioned by International Probiotics Association (IPA), analysed the global clinical trials with probiotics and observed that over 1,600 clinical studies were registered at ClinicalTrials.gov and/or the International Clinical Trials Registry Platform (ICTRP) of the World Health Organisation (WHO). These trials address over 700 different and specific outcomes such as gastrointestinal (GI) diseases and conditions, neurological conditions, metabolic syndrome related conditions, improving immunotherapies for cancer, modulation of microbiota for a host of many other conditions etc. For the most recent studies with probiotics, a shift can be noted towards non-gastrointestinal conditions, with top three conditions being communicable diseases (with 15 studies), infection (15) and metabolic diseases (12). At strain level, Lactobacillus rhamnosus GG was the probiotic strain most frequently registered (146 studies), followed by Bifidobacterium animalis ssp. lactis BB12 with 55 studies. VSL#3, a consortium of 3 different Bifidobacteria, 4 Lactobacilli, and 1 Streptococcus thermophilus strain was the most registered multispecies preparation in 74 studies.
Elaborate safety assessments and clinical studies will be required for the novel probiotic strains with no history of use. High R&D costs for strain level characterisation and clinical studies for health claim validation, as well as non-harmonised regulations for probiotics product approvals across the markets will remain major challenges for the industry.
Product Development
The probiotics product development has evolved over the decades, starting from the use of single cultures, stabilised cultures, use of various delivery methods and use of blends/formulations. Stability was the key for all the formats. Different strategies have been used to improve the probiotic stability during food manufacturing processes. These include (i) technological approaches such as the modification of production parameters, (ii) the reformulation of products such as encapsulation, (iii) delivery technologies such as controlled/ time of consumption release and (iv) microbiological approaches focused on selecting strains with resistance. The demand for probiotics is also driving the focus on quality assurance for viability, dose levels and functional integrity.
The microbial composition of probiotic products range from a single strain to multi-strain or multi-species compositions and combination of strains with prebiotics/ minerals (synbiotics). Evidence shows that the gut microbiome influences the host physiology by regulating metabolism, immunity and the gut-brain axis via signalling of microbiome-generated bioactive metabolites. Emerging concepts and new approaches to modulate microbiomes such as postbiotics and microbial consortia are expected to drive the probiotics industry.
Postbiotics are “a preparation of inanimate microorganisms and/or their components/ metabolites that confer a health benefit on the host”. Some of the novel and promising strains may be commercialised as postbiotics, like the use of pasteurised A. muciniphila for beneficial effects.
Conclusion
The advances in modern biology, bioinformatics and data analytics are likely to provide greater insights on probiotics and related concepts. There is a need for intense research on emerging concepts related to probiotics, establishment of regulatory frameworks to assess and approve novel concepts, as well as a need for harmonisation of probiotic regulations across markets.