Safety assessment of probiotics for human use

Abstract

The safety of probiotics is tied to their intended use, which includes consideration of potential vulnerability of the consumer or patient, dose and duration of consumption, and both the manner and frequency of administration. Unique to probiotics is that they are alive when administered, and unlike other food or drug ingredients, possess the potential for infectivity or in situ toxin production. Since numerous types of microbes are used as probiotics, safety is also intricately tied to the nature of the specific microbe being used. The presence of transferable antibiotic resistance genes, which comprises a theoretical risk of transfer to a less innocuous member of the gut microbial community, must also be considered. Genetic stability of the probiotic over time, deleterious metabolic activities, and the potential for pathogenicity or toxicogenicity must be assessed depending on the characteristics of the genus and species of the microbe being used. Immunological effects must be considered, especially in certain vulnerable populations, including infants with undeveloped immune function. A few reports about negative probiotic effects have surfaced, the significance of which would be better understood with more complete understanding of the mechanisms of probiotic interaction with the host and colonizing microbes. Use of readily available and low cost genomic sequencing technologies to assure the absence of genes of concern is advisable for candidate probiotic strains. The field of probiotic safety is characterized by the scarcity of studies specifically designed to assess safety contrasted with the long history of safe use of many of these microbes in foods.

Impact of probiotic supplements on microbiome diversity following antibiotic treatment of mice

“…29,30 Commonly used probiotic strains have also been documented to contain antibiotic resistance genes which could create a potential source for transfer of resistance to other members of the microbial flora. 46 In some rare incidents, such as patients with underlying medical conditions, the probiotic strain can become the pathogen causing an adverse event. [47][48][49] Collectively, a better understanding of the impacts of probiotics on the microbial flora is required to ascertain how best to use them to treat disease.…”

Extensive Horizontal Gene Transfer in Cheese-Associated Bacteria

“…In addition to starter cultures used for fermented foods, living microbial supplements ('probiotics') are increasingly being adopted in agriculture (Verschuere et al, 2000;Chaucheyras-Durand and Durand, 2010) and for a wide range of human health conditions (Cuello-Garcia et al, 2015;Onubi et al, 2015; (IBS Dietetic Guideline Review Group on behalf of Gastroenterology Specialist Group of the British Dietetic Association) et al, 2016), and even as cosmetics (Whitlock et al, 2016). The need to screen for clinically relevant elements such as antibiotic resistance genes is widely recognized (Sanders et al, 2010), but other mobile gene elements from these organisms may also enter native microbial populations with unknown consequences.…”

Bioengineered probiotics, a strategic approach to control enteric infections

“…Prior to the approval of a recombinant probiotic for human use, it is essential that the bacteria be screened for potential pathogenicity and virulence traits. 10,21,99 Providing evidence for the absence of virulence properties is relatively straightforward in elucidating the pathogenic potential. Besides phenotypic characterization, it is also essential to genetically screen potential candidates for use as probiotics.…”

“…Therefore, when intended for use as drugs, the safety assessment must balance risk with benefit. 99 Another important consideration for genetically modified probiotic is preventing its accumulation in the environment and preventing lateral dissemination of the genetic material to other bacteria. The best approach to address this concern is to use a biological system that is propagated along with the probiotic termed as biological containment systems.…”