Dr. Manish Bhatnagar details the safety and efficacy of pre and probiotics and the current challenges in usage. He also writes the precautionary measures that need to be taken while using them.

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Evidence of safety & efficacy

Sanders et al stated that most probiotics in use today are derived either from fermented foods or from the microbes colonising a healthy human and have been used in products for decades. On the basis of the prevalence of Lactobacilli in fermented food, as normal colonisers of the human body, and the low level of infection attributed to them, their pathogenic potential is deemed to be quite low by experts in the field.

Bifidobacterium species enjoy a similar safety record. Most products are designed for the generally healthy population, so the use in people with compromised immune function or serious underlying disease is best restricted to the strains and indications with proven efficacy. Microbiological quality standards should meet the needs of at-risk patients, as reviewed.

Vandenplas Y et al study concluded that probiotics are generally regarded as safe, and side effects in ambulatory care are seldom. Large-scale epidemiological studies in countries where probiotic use is endemic demonstrate low rates of systemic infection in adults, between 0.05 and 0.40%. Saccharomyces fungemia secondary to use of the probiotic has been described in critically ill patients who were receiving nutrition enterally or with a central venous catheter. Probiotics should be carefully used in hospitalised patients. A cautious assessment of the risk-benefit ratio must be made. To ensure patient safety, probiotics should be properly handled during administration.

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Strength and use

There is no evidence from comparative studies to rank the products in terms of efficacy.

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Challenges for pre-probiotic usage

The microbiome is potentially ready for therapeutic benefit. Since diet seems to be the overriding factor in the long-term stability of the microbiota, methodologically rigorous evaluation of diet will be important. Both IBD and IBS have uncertain causes and the insights gained from this investigative process will undoubtedly shed new light on their genesis and reveal new approaches to prevention, as well as treatment.

However, with all the factors affecting probiotic therapy, it has been shown to be beneficial to have probiotic formulations that incorporate both pharmaceutic and commercial food-based ingredients together to have an effective dosage form for the delivery of probiotics to not only the intestinal system but as well as the urogenital system. It should be emphasised that probiotics are viewed as food and not drugs by the medical community. There is a need for a robust evidence-based approach to convince the clinical community of the health benefits of probiotics.

These agents will need to demonstrate their effectiveness within existing regulatory frameworks such as:

• The traits that underline prebiotics’ function will need to be understood
• Different strains must be compared at the gene level in vitro
• Natural strains should be selected for specific gene products to improve probiotic function
• Optimal natural strains need to be determined
• Clinical documentation of the effect of probiotic strains must be provided

The clinical evidence needs to be appraised in a different manner than concerning drugs and therapeutics in order to demonstrate that they can enhance the proliferation of beneficial microbes and thus produce sustainable changes in the human microbiome. There are many potential advantages of probiotics over conventional therapy, including relatively low cost, the fact that probiotics are unlikely to increase the incidence of antibiotic resistance and the multiple mechanisms by which probiotics presumably inhibit pathogens, thereby decreasing the chances for development of resistance against the probiotic.

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Gap in today's probiotics

The major disadvantage with probiotics is that they are Genetically Modified Organisms (GMOs) and as such their use in the treatment of humans would essentially constitute the deliberate release of such a GMO into the environment. Therefore the safety of such strains needs to be guaranteed and stringently monitored so that they do not:

• Possess antibiotic selection markers
• Have the ability to accumulate in the environment
• Transfer the genetic modification to other bacteria through lateral dissemination

Biological containment can be divided into active and passive forms. Active containment is conditionally controlled by the production of a compound that is toxic to the cells. Gene expression is tightly regulated and controlled by an environmentally responsive element. Passive containment meanwhile, is dependent on complementation of an auxotrophy by supplementation with either an intact gene or the essential metabolite.

The future use of probiotics as vectors targeted to gastrointestinal mucosal lesions is promising. This new targeted drug delivery approach using probiotics is known as “pharmabiotics”.

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Caution advice

In the context of probiotics usage, caution needs to be taken by everyone who chooses to take these supplements, but this is especially true for children, pregnant women, elderly people and people with compromised immune systems. For people with compromised immune systems due to disease or treatment for a disease (such as cancer chemotherapy), taking probiotics may actually increase one’s chances of getting sick. It has been shown that the use of various probiotics for immunocompromised patients or patients with a leaky gut has resulted in infections and sepsis (infection of the bloodstream).

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Conclusion

Current global research efforts have validated the role of GI commensal organisms/gut microbiota and their strange symbiotic association with humans. Evidence is gradually developing for the potential of probiotics and prebiotics to impact other conditions of the GI tract, such as IBD, constipation, IBS and colon cancer as well as extra-intestinal infections. When prescribing probiotics, one must consider the probiotic formulation, including live, dead, compounded preparations or their products, the effective dose to use and the type of disease targeted.

In summary, future large-scale clinical trials controlling dosing, viability and other critical variables will be crucial to provide the necessary scientific evidence required to determine the efficacy of the ever-increasing use of probiotics. Newer indications like Foecal Microbiota Transplant (FMT) in C.difficile diarrhea and IBD are expanding the frontiers of pre-probiotics use.

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Are bugs better than drugs?

Evidence is now building up to show that gastrointestinal immune health is dependent and influenced by the gut microbiota “Designer Probiotics” that are target-specific/disease-specific will probably be the future direction of research.

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. Manish S Bhatnagar is a Consultant Gastroenterologist, Hepatologist and Therapeutic Endoscopist from Ahmedabad.