Probiotics: Side Effects and Safety

What are Probiotics?

The word probiotic which means ‘ for life’ was coined in 1965 by Lilly and Stillwell [1] and is defined as live microorganisms, which when administered in adequate amounts confer a health benefit on the host. Probiotics are essentially the microorganisms that are normal commensal residents of our gastrointestinal tract. The most common probiotic strains belong to the genera Lactobacillus and Bifidobacterium.  Common Lactobacillus probiotic strains include L. acidophilus, L. casei, L. rhamnosus, and L. reuteri.  Bifidobacterium probiotic strains include B. bifidum, B. longum, and B. infantis.




Probiotics have gained immense popularity and their sale is rising as more and more people are becoming aware of their health benefits. Probiotics are available in the market as proprietary dietary supplements (as a single strain or a combination of different strains) and in the form of fermented foods such as yogurt, kefir, sauerkraut and kimchi.Probiotics

Probiotics have been shown to confer health benefits by aiding in functions such as digestion, preventing pathogens from invasion [2], [3], supporting immune functions [4], enhancing intestinal barrier5], production of antimicrobial substances [6], production of short chain fatty acids important for growth of colonic cells [7] and improving overall microbial balance in the gut. Probiotics has also been investigated for their potential role in improving oral health [8].

Extensive research has been carried out to examine the potential effects of probiotics in mitigating diseases including gastrointestinal diseases such as Irritable bowel syndrome (IBS) [9], Inflammatory bowel disease(IBD) [10, lung diseases [11], central nervous system conditions [12], [13], liver diseases [14], metabolic diseases [15] and cancer [16]. Thus, probiotics seem promising candidates for treating or preventing health problems.

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Safety of Probiotics

With so much effort and attention diverted towards demonstrating the health benefits of probiotics, examining the potential side effects of probiotics are often underestimated. Although the existing clinical data provides evidence of no increased risk of probiotics use, there are not enough studies that address important aspect of probiotic use. Overall, probiotics have been considered safe and have been used in many clinical cases. However, in some cases, adverse effects of probiotics have been also observed.

  1. Fungemia

A report released by World Health Organization (WHO )in 2002 stated that  probiotics may be responsible for four types of side effects [17]. These include: 1) systemic infections, 2) deleterious metabolic activities, 3) excessive immune stimulation in susceptible individuals and 4) gene transfer. Several case studies reported that administration of probiotics Saccharomyces boulardii resulted in fungemia in patients suffering from different conditions [18], [19], [20], [21], [22].

  1. Bacteremia and Sepsis

Lactobacillus strains on one hand have been shown to confer protective effects in various patients but on the other hand have caused systemic infections and other complications. In a study, administration of Lactobacillus rhamnosus to children with acute diarrhea resulted in shorter duration of diarrhea, less chance of a protracted course, and faster discharge from the hospital [23].  In another study, Lactobacillus rhamnosus GG was found to reduce antibiotic-associated diarrhea in children treated with oral antibiotics for common childhood infections [24]. Other similar reports have  demonstrated the protective effects of Lactobacilli [25], [26].  In contrast, some case studies have reported bacteremia  in patients after they ingested strains of Lactobacilli genus such as L.rhamnosus [27], [28], [29], L. acidophilus [30] and L.casei [31]. Bacteremia was found to be associated with the use of other probiotics as well. One case of sepsis caused by Bifidobacterium breve was reported [32] .Two cases of Bifidobacterium longum bacteremia were reported in newborns receiving probiotics [33]. Another case reported septicemia in response to probiotic Bacillus subtilis [34].

  1. Endocarditis

Endocarditis, an inflammation of the inner layer of the heart, was also reported to be associated with probiotic use. A study reported that consumption of a freeze-dried probiotic preparation containing Lactobacillus rhamnosus in a subject caused endocarditis [35]. Another study revealed that  a subject who consumed large quantities of probiotic yogurt developed endocarditis and septic arthritis caused by Lactobacillus rhamnosus [36].



  1. Can Cause Death

A randomized, double-blind, placebo-controlled trial examined the effect of multispecies probiotic preparation in patients with predicted severe acute pancreatitis (n=153) vs placebo (n=145). In this study, nine patients in the probiotics group developed bowel ischemia (eight fatal), compared with none in the placebo group. Use of probiotic was found to be associated with an increased risk of mortality in this study [37]. These studies suggest that probiotics should be used with caution in human subjects especially in immunocompromised, hospitalized patients and infants. A detailed assessment of a probiotic strain to be used in patients should be carried out.

  1. Drug Resistance

Another significant concern regarding the safety of probiotics is their ability of gene transfer. Species of genus Lactobacillus are known to carry plasmids containing chloramphenicol resistance [38], tetracycline resistance [39] and erythromycin resistance [40]. Plasmids are commonly found naturally occurring autonomous DNA molecules in bacteria that replicate independently of chromosomal DNA. A study demonstrated in mice, transfer of gene for vancomycin resistance (vanA) from an Enterococcus strain to L. acidophilus, providing evidence that transfer can take place in the gut [41].

One should also keep in mind that a probiotic strain or a combination of few strains which has been well studied in isolation may have different effects when it is administered in human or animal subjects owing to the complex nature and interactions of the gut microbial community. Although, some underlying mechanisms of how probiotics function are known, a detailed understanding of these mechanisms is still lacking thus complicating the predictability of the safety of a probiotic strain. Then there is an issue of presence of unlabeled microorganisms that are not indicated on the label of retail probiotics. Investigations using culture dependent and culture independent approaches have revealed these findings [42], [43], [44]. This misrepresentation can potentially increase the unknown risk associated with a given probiotic supplement.  In addition, reagents used in the production of probiotics and which are not properly labeled can also pose serious threat as exemplified by the case of anaphylactic reactions in two different case studies [45], [46].

Conclusion

Probiotics are proving to be very promising candidates for treating or preventing diseases. The existing data largely supports their efficacy and safety. However, not much attention has been devoted to understanding their safety and much works need to be done to evaluate this criteria. Studies are necessary to understand in details the underlying mechanisms of probiotic actions. Clinicians should more carefully assess the risks and benefits of probiotics before they can be prescribed. In general, probiotic supplements are not monitored strictly and thus the safety of these supplements in not guaranteed. Thus, one should be cautious and thorough in choosing these supplements when considering their use.



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About DrGoel 29 Articles
Doctor by profession and more than a decade of practice behind her Dr Goel occasionally writes to bring awareness on various diseases and conditions.

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