Probiotics have been rising in popularity, and are known for a abundance of health benefits, some backed up with

scientific
evidence [1]. However, as research progresses, there are also safety concerns around the use of probiotics. The main con-
cerns are diseases as bacteraemia and endocarditis, release of toxic, negative metabolic effects on the gastrointestinal trac
and antibiotic resistance gene transfer [2]. In this overview the safety concerns around probiotics will be discussed.

SAFETY GUIDELINES GENERAL SIDE EFFECTS MISLABELLING

Probiotics are controlled in the European Union by There are four categories of side effects from probi- Mislabelling is a safety concern among probiotics. It
the Novel Foods Regulation. A GRAS (Generally As otics [5] has been reported in three ways; wrong numbers
Safe) status is given to microorganism strains when of organisms, incorrect bacteria labelled, and mis-
 Systemic infections
no safety concerns have been found. However, the spellings. Research has found that on 32% of the
 Metabolic and enzymatic effects
adverse effects of probiotics are little understood [3]. labels misspelling occurred, when testing bacteria
Probiotic strains are characterized by a variety of  Immunomodulation and adjuvants
accuracy only 27% met or exceeded the claims
experiments to develop safety standards for probiotic  Gene transfer
they made on the label regarding amounts and
microorganisms. These tests include, antibiotic toler- These do not occur with all strains of bacteria nor in species. In total only 8% had an accurate and ade-
ance, metabolic activity, toxin development, haemo- every individual. Of these four categories infection is quate label, meaning specific and valid bacterial
lytic activity, infectivity in immunocompromised ani- most common, where immunocompromised indi- names including genus and species, no spelling
mal models, side effects in humans and adverse viduals are at greater risk, for example at endocardi- errors and clear number of organisms mentioned
outcomes in consumers [4]. tis [6]. [7].
SPECIES WITH SAFETY CONCERNS
Table 1. an overview of some of the safety concerns regarding species of bacteria used in probiotics
Genus Species Safety concerns
E. faecium - Urinary tract infection - Endocarditis
Enterococcus E. faecalis - Intra-Abdominal and Pelvic Infection - Skin and Soft Tissue Infections
- Bacteraemia - Meningitis (rare cases) [10]
S. salivarius - Meningitis
Streptococcus S. vestibularis - Endocarditis
- Bacteraemia [8]
B. cereus - 2 food-borne illnesses
- emetic (vomiting) illness
- diarrheal infection [5]
Bacillus B. licheniformis - Producers of heat-stable or heat-labile toxins
B. clausii
B. subtilis
B. pumilus [11]
E. coli - Sepsis
Escherichia - The administration of the Nissle 1917 probiotic E coli strain to people with compromised immune
systems can cause significant negative effects. [5]
L. rhamnosus - Abscesses
(strain: GG) - Bacteraemia > Causing: clinical illness, including fever, elevated leukocyte counts, and elevated C-
Lactobacillus reactive protein values [12]
- Sepsis cases are reported in preterm infants; however research has not been able to find a link to a
significant increased of infection after administration of probiotics. [13]

GENERALLY REGARDED AS SAFE ANTIBIOTIC RESISTANCE

Some bacteria that are generally regarded as safe include the
Lactococcus, Lactobacillus (species, acidophilus, casei, fermentum,
gasseri, johnsonii, paracasei, plantarum, rhamnosus, and salivarius)
and Bifidobacterium (species, adolescentis, animalis, bifidum,
breve, and longum) [14]. Bifidobacterium is one of the safest
genuses to be used as a probiotic and the chances of be-
ing severely infected in healthy consumers are very small [15].
There have been cases reporting infection caused by these bacte-
ria, however these cases are mostly in the immunocompromised
population. Research shows that the risk of infection with strains of
these bacteria is equal to the risk of infection with commensal
strains [5]. Also the Streptococcus Thermophilus species is often
used in probiotics, and is considered to be safe for utilisation as a
probiotic [16]. However, research is still conflicted as there have
also been negative effects found for GRAS identified strains
Enterococci strains are the
third most common microor-
ganism in bloodstream infec-
tions [10]
Probiotics are defined as
“live microorganisms which
when administered in ad
quate amounts confer a
health benefit to the
host.” [17]
Another safety concern lies with the concept of antibi-
otic or antimicrobial resistance. Probiotics are often
taken in conjunction with antibiotics to regulate the gut
microbiome. Therefore, they should be resistant to
antibiotics. This resistance can occur in 2 types; intrinsic
resistance and acquired resistance. Intrinsic meaning it
is a naturally occurring trait, acquired meaning it derives
from genetic mutation or acquisition of foreign DNA f
rom other bacteria [5]. The fact that this resistance can
be acquired is a problem. If the antibiotic resistance in
the bacteria of the probiotic is transmissible, the gene
might be transferred to pathogenic bacteria, therefore
allowing them to be resistant to antibiotics and posing
serious clinical consequences [2].