Antimicrobials With Probiotics as Potential Antimacrobials
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"Obviously, bacteria used in probiotic products should not inhibit the growth of other probiotic strains. However, one of the most dangerous traits of bifidobacteria and LAB is the potential transfer of antibiotic resistance genes to pathogenic bacteria within the gastrointestinal flora (Teuber et al. 1999). A European Food Safety Authority (EFSA) document recommends that commercial strains used in the production of food supplements should not harbour transferable antibiotic resistance; for this reason, EFSA guidelines strongly recommended that minimum inhibitory concentrations (MICs) of the most important antimicrobial agents used in human care be evaluated (EFSA 2008). Many routes of antibiotic resistance transfer exist: integrons, transposons, insertional elements, bacteriophages and conjugative plasmids are all implicated in such mechanisms (EFSA 2008). The intense use of antimicrobial agents for medical use and also in animal husbandry has led to the selection of antibiotic-resistant strains within the gut microbiota of humans and livestock; consequently, in the last decades, there has been a massive spread of antibiotic-resistant bacteria worldwide (Devirgiliis et al. 2011)."
Antibiotic resistance propagation through probiotics
"With the discovery of the transfer of gene content containing antimicrobial resistance (AMR) genes to other microorganisms (primarily through mobile genetic elements or plasmids), there has been speculation that this complication may also occur as a side effect of probiotics, especially in the longtime use [10]."
"Alarmingly, in-vitro and in-vivo studies proved that carrying resistance genes by probiotics and, as a gene reservoir, are capable of transferring AMR genes to other present microorganisms such as the normal microbiota or pathogenic bacteria in the intestine, oral, and vaginal cavities [15,16,17]."
"Probiotics are associated with various types of adverse events, and according to the safety regards, performing some tests such as toxin production, hemolytic potential, antibiotic resistance, and analyzing metabolic activities are recommended [48]. Bacteremia, fungemia, GI ischemia, diarrhea or constipation, bloating and flatulence, skin rashes or skin acne, metabolic problems such as D-lactic acidosis, extreme immune stimulation, endocarditis, AMR, etc. are correlated with the consumption of different species of probiotics in human [8]. The exact mechanism of probiotics' adverse effects is still unknown that increases the current concern of scientists. However, it is reported that if the endogenous microbial community cannot occupy all functional niches in the target site (e.g., intestine), the available niches can be occupied by the pathogens and may lead to infection [1]."
"[..]due to the involvement of antibodies in the etiology of IBD, the immune-stimulatory property of probiotics can worsen the situation and the immunocompromised patients are at higher risk of infections caused directly or indirectly by probiotic bacteria [87]."
"Moreover, during antibiotic treatment, which establishes an imbalance in the microbiota, colonization of pathogenic bacteria is escalated. It provides an environment to transfer genetic content among available microorganisms such as pathogenic bacteria, probiotics, and the normal microbiota. HGT [Horizontal Gene Transfer] among existing microorganisms (donors or recipients) leads to resistance toward a wide range of antibiotics."
"Molecular studies reported sequence similarities between resistance genes in different bacteria and identical sequences in gram-positive and gram-negative bacteria, which shed light on the transfer of mutant genetic content across the mentioned microorganisms. Although different strains of probiotics carry specific resistance genes, they are capable of transferring to other microorganisms. Taken all together, this review supports the double-edged impact of probiotic consumption, and taking adequate precaution for the prevention of probiotics’ wide-spreading side effects is recommended."
Involvement of Probiotics and Postbiotics in the Immune System Modulation
"For the beneficial effects of probiotic microorganisms to be seen, it is recommended that the number of viable cells reaching the intestine should be at least 10^6–10^7 colony-forming units (cfu)/g [125]. However, in most commercial probiotic products, many beneficial microorganisms, especially near the end of their shelf life, lose their “viability” [126]. Therefore, probiotic products are produced to contain more microorganisms (on average 2.5 times) than the number of live probiotic microorganisms written on the label."
"Interestingly, studies found that when probiotics were administered in humans following antibiotic therapy, the increase in probiotic strain-induced colonization in the colon microbiota was associated with persistent or prolonged dysbiosis [131,137]."
"The latest Cochrane report states that probiotics are successfully used to prevent infectious diarrhea in both children and adults [138]. However, there are also studies reporting cases of bacteremia, sepsis, fungemia, endocarditis, meningitis, endometritis, peritonitis, and pneumonia as a negative consequence of probiotic administration [139]. This pathological phenomenon may develop due to an impaired gut barrier, immunosuppression, or leaky gut conditions [140]. It has been suggested that factors facilitating translocation by probiotics may be linked to the intestinal mucosal adhesion capacity or mucolytic activity [141,142]."
"Evidence suggests that microbial vitality is not required to achieve health benefits as with probiotic supplements and postbiotics produced from probiotics provide similar health benefits to probiotics [149]. Despite various health benefits, postbiotic ingredients derived from probiotics are thought to be promising alternative supplements to eradicate the above-mentioned risky conditions of probiotics [150]."
"Some postbiotics are cell-free supernatants, vitamins, organic acids, SCFA, secreted proteins/peptides, bacteriocins, neurotransmitters, secreted biosurfactants, amino acids, flavonoids derived from postbiotics (desaminotyrosine, equol daidzein, daidzein, and norathyriol), postbiotics derived from postbiotics (genipin, paeoniflorin, paeoni lactone glycosides, paeonimetabolin I, II, and III), metabolites of probiotic microorganisms such as phenolic-derived postbiotics (equol, urolithins, valerolactones, enterolactone, enterodiolen, and 8-prenylnarenin) and teichoic acids, peptidoglycan-derived muropeptides, molecules protruding from the surface (pili, fimbriae, and flagella), exopolysaccharides (EPS), cell surface related proteins, and inactivated/dead/non-viable microbial cell components of probiotics, such as cell wall-bound bio-surfactants [154,155]."
"In addition to eliminating the disadvantages of probiotics for microbiota and the immune system, postbiotics can also reduce the use of food additives because they act as emulsifiers and preservatives in ensuring the stability of the products they are used. There is also some evidence about immunomodulatory and the therapeutic effects regarding products containing commercial postbiotics. Although the use of them in the food and pharmaceutical industry is promising, more studies are required to avoid the side effects and disadvantages that may occur with the use of products containing probiotics, especially in people with a weak immune system."
