Complimenting Antibiotics with Probiotics: Your Essential Guide
FEATURE
Ashton J Harper
Antibiotics revolutionized twentieth-century medicine and have continued to be embraced as powerful allies in our modem existence. Thus, it comes as no surprise that they are some of the most prescribed drugs in the world.1 They are responsible for saving countless lives, yet their vast and frequently indiscriminate use, combined with a deficit of new antibiotics,2 has led to the current global health threat of antibiotic resistance.3 The problem does not end here because antibiotics also have a number of unfortunate side effects, including antibiotic-associated diarrhea and candidiasis4 and the possible development of a number of chronic diseases, including irritable bowel syndrome (IBS),5 obesity,6 allergies,7 and even psychiatric disorders.8 Probiotics present a logical and natural solution to reduce the disruption caused by antibiotics and return the gut microbiota back to baseline following such treatment. Probiotics have demonstrated benefit as an adjunctive treatment with antibiotics to enhance efficacy,910 and they reduce side effects in a range of conditions.1112
* * Recent meta-analyses on this topic have concluded that probiotics may reduce the relative risk of AAD by 42%, and cases of CDAD by 64%. JJ
Antibiotic-associated diarrhea and Clostridium difficile infection
Antibiotic-associated diarrhea (AAD) may result from a disturbance in the composition and functionality of the gut microbiota. Our resident gut flora is responsible for, among many other roles, bile acid and carbohydrate metabolism, and impairment of these processes may lead to secretory and/ or osmotic diarrhea.13 Collateral damage to our commensal
■ "Inflammation has been identified as a risk factor for neurodevelopmental and neuropsychiatrie disorders, ranging from autism spectrum disorder to major depression. J J
microbes, a common problem with broad-spectrum antibiotic use, may abolish colonization resistance resulting in overgrowth of pathogenic bacteria and a toxin-mediated AAD, as seen in Clostridium difficile (C. difficile) diarrhea.14Furthermore, some antibiotics, such as the tnacrolide erythromycin, may exert a direct stimulatory effect, via motilin receptors, that induces diarrhea.13 The incidence of AAD ranges from 5 to 62%15 in
the general population and may occur at any time from start to two months after antibiotic completion. It is the most frequent intestinal complication following antibiotic use, especially for broad-spectrum antibiotics,16 and children under the age or two and the elderly are at highest risk.
AAD severity may range from mild and brief diarrhea to the life-threatening pseudomembranous colitis caused by C. difficile,17 Overgrowth of this bacteria may be the cause of AAD in 15 to 39% of those over 65 years of age,18 where it may prove fatal in as much as 7% of cases.19 20 In children, the presence of C. difficile is more commonly community acquired, with far fewer cases of severe diarrhea compared to the elderly.21
Probiotics in the prevention of AAD and CDAD
Probiotics may prevent AAD and CDAD by numerous mechanisms, such as stabilizing the barrier force of the resident microflora, augmenting various immune functions (e.g., increasing secretory IgA levels or inducing increased output of antitoxin antibodies), direct antimicrobial abilities (e.g., bacteriocin production), and maintaining homeostatic intestinal physiology (e.g., enhancement of ectomembrane enzymes).16 An overwhelming number of human trials have identified the clinical efficacy of probiotics in the management of these diseases.22 23 Recent meta-analyses on this topic have concluded that probiotics may reduce the relative risk of AAD by 42%,22 and cases of CDAD by 64%.23 This evidence is compelling and it is enabling healthcare professionals in all disciplines to conclude that probiotic adjuncts are capable of reducing the significant morbidity and mortality associated with these common complications.
However, it is important to note that some probiotic preparations have failed to reduce the risk of AAD.24-25 Probiotic products aie highly variable and evidence of strain-specific properties must be appreciated.26 It is very possible, therefore, that certain bacterial strains, or combinations of strains, lack the required functional profile to prevent AAD.27 Interestingly, numerous studies have suggested that multi-strain preparations may be superior to single-strain products in AAD and CDAD prevention, potentially benefiting from enhanced diversity and synergism.28 30
Antibiotic complications beyond AAD
A growing body of evidence suggests
Human clinical trials have shown that probiotics may improve the efficacy of and/or educe the adverse effects of antibiotic treatment, thus helping to maximize the eradication success with the initial course. J J
that the dysbiosis caused by antibiotics may also have a chronic impact on human health.
Antibiotic usage was shown to be associated with IBS development in a study involving more than 26,000 adults.5
In a recent Danish study, which examined more than 28,000 mother-child dyads, antibiotic use during the first six months of life was shown to increase the risk of children being overweight (born to normal weight mothers). The authors suggested that this effect may be explained by an impact on the diversity of the microbiota and highlighted the potential utility of probiotics as a preventative measure.6
Astonishingly, up to 50% of laboring women and neonates receive antibiotics. This exposure may have detrimental impacts on gene expression and immune system development that could explain the rise in allergic diseases in recent times.7 Probiotic therapy in this setting may help to modulate the immune system16 and prevent the development of atopy in later life.
Inflammation has been identified as a risk factor for neurodevelopmental and neuropsychiatrie disorders, ranging from autism spectrum disorder to major depression. Regulatory T cells (Treg), specific populations of which have been shown to be induced by a number of Lactobacilli and Bifidobacteria species,8 play an important role in regulating the immune system and inflammatory responses. Interestingly antibiotic treatment appeal s to deplete this vital population of lymphocytes and lead to the enhanced production of proinflammatory cytokines. Multiple
probiotic species have been shown to have stress-protective and mental health benefits in both animal and human trials.8
Antibiotic resistance
The current global concern over antimicrobial resistant bacteria is well warranted. In the United States alone, at least two million people develop infections each year from antibioticresistant bacteria, which are responsible for a staggering 23,000 annual deaths.31 This situation poses a significant public health threat on a mass scale. In the past decade alone, there has been a significant increase in the magnitude of antibiotic resistant organisms.3 Multi drug-resistant tuberculosis (MDR-TB), methicillin-resistant Staphylococcus aureus (MRSA), and carbapenem-resistant Klebsiella pneumoniae are concerning examples of difficult-to-treat antibiotic-resistant bacterial infections.132 The exposure of these organisms to antibiotics creates the selective pressure required for the emergence of resistant strains, which, combined with the long-standing, pervasive and injudicious use of antibiotics, has accelerated the process.3 An important element here is the failure to complete a full course of antibiotics for reasons such as allergic side effects, secondary infections, and AAD.33’34 This situation exposes pathogens to sublethal doses, which allows resistant populations to evolve and flourish. Antimicrobial stewardship aims to halt or at least slow the generation of resistant pathogens and involves strict regulation over timing, selection, dosage, route, and duration of antibiotic treatment.2 It is clear, however, that these measures alone may not be enough,35 thus prompting the need for additional therapeutic strategies such as probiotics.36
Probiotics in the prevention of antibiotic resistance
Human clinical trials have shown that probiotics may improve the efficacy of and/or reduce the adverse effects of antibiotic treatment, thus helping to maximize the eradication success with the initial course. Evidence of this benefit has been demonstrated in the treatment of Helicobacter pylori,37 amoebic dysentery,38 bacterial vaginosis,12 and urinary
tract infections.10 The advantage gained here is the reduction of repeated exposure to further courses of antibiotics, which is known to contribute to resistance.36 Similarly, the prevention of antibiotic side effects, such as AAD, should improve compliance to treatment and thus also prevent pathogens from being exposed to sublethal dosages, which further promotes resistance. Probiotics are thus a worthy ally in our battle against antibiotic resistance, with evidence of benefit in reducing both morbidity and healthcare costs.25
The role of chiropractors in the reduction of antimicrobial resistance
Antibiotic resistance is one of the most dangerous threats to human health, and as such, healthcare practitioners and the general public must take responsibility to curb the problem. As chiropractors, you are perfectly positioned to educate your patients in the proper use of antibiotics and to offer them options to mitigate and reduce the frequently encountered side effects.
A survey conducted in 2,000 adults this year (OnePoll, UK survey) found that 50% of people expressed concerns about the side effects of antibiotics, and 15% admitted having experienced diarrhea after taking antibiotics. More than 80% of responders were willing to take probiotics alongside antibiotics if their healthcare practitioner advised them they could help reduce the number of repeated courses of antibiotics or decrease the risk of antibiotic-associated side effects. If the general public are prepared to take measures to solve the antibiotic crisis, then we as practitioners need to be able to offer safe and sensible options.
Human clinical trials912 have demonstrated that highquality multi-strain probiotics, taken alongside antibiotics, provide a safe and successful option to reduce the side effects and improve the efficacy of antibiotics. This, in addition to the potential of combating antibiotic resistance, and preventing the associated chronic health conditions associated with antibiotic usage, makes the adjunctive use of probiotics well recommended.
SEE REFERENCES ON PAGE 60...
Dr. Ashton Harper obtainedaB.Sc. degree inphysiol ogy and pharmacology in 2007from University College London where he later graduated in 2010 in medicine. He worked in the NHSfor 5 years during which time he discovered his passion for the management of gastro intestinal diseases. Whilst working in gastrointestinal
surgery he achieved membership of the Royal College of Surgeons and was awardedapost-graduate travellingfellow ship to visit the Cleveland Clinic in the USA to observe world leading doctors man age inflammatory bowel disease. He has published in the fields of nutrition and gastrointestinal diseases and has presented his work at multiple national and international medical congresses. Ashton has joined the industry as aMedicalAdvisor for the Protexin Hu man Healthcare team where he is responsibleforproviding medical expertise for the business.
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