|Year : 2022 | Volume
| Issue : 1 | Page : 12-17
Intestinal side effects of improper antibiotic use: Cause, symptoms, and treatment through probiotic food sources
Faculty of Pharmacy, Cyprus International University, Lefkosa, Mersin, Turkey
|Date of Submission||29-Jul-2021|
|Date of Acceptance||22-Jan-2022|
|Date of Web Publication||29-Jun-2022|
Mr. Amirabbas Nikmaram
Faculty of Pharmacy, Cyprus International University, Lefkosa 99010, Mersin
Source of Support: None, Conflict of Interest: None
When antibiotics emerged, they gained lots of interest on the basis that they could protect and help human beings against a variety of bacterial diseases. These include urinary tract infections, pneumonia, sinus infections, etc. However, they have the potential to cause undeniable side effects including the drastic alter of gut microbiota. Antibiotic-associated diarrhea, nausea, vomiting, and other gastrointestinal side effects could also result from these alterations in gut microbiota. To diminish these side effects, the use of probiotics was proposed. Probiotics are defined as live microorganisms that have health benefits for the host by countervailing the bacteria which were lost in the gut, and they can be gained through different resources such as supplemented capsules and foods (especially dairy products). In this review, we discussed the antibiotic-associated side effects which can be treated or prevented by consuming probiotic foods.
Keywords: Antibiotics, dairy products, gut dysbiosis, gut microbiota, nutrition therapy, probiotic
|How to cite this article:|
Nikmaram A. Intestinal side effects of improper antibiotic use: Cause, symptoms, and treatment through probiotic food sources. J Rep Pharma Sci 2022;11:12-7
|How to cite this URL:|
Nikmaram A. Intestinal side effects of improper antibiotic use: Cause, symptoms, and treatment through probiotic food sources. J Rep Pharma Sci [serial online] 2022 [cited 2022 Nov 29];11:12-7. Available from: https://www.jrpsjournal.com/text.asp?2022/11/1/12/348868
| Introduction|| |
Since Sir Alexander Fleming developed the first antibiotic in 1928 (penicillin), hundreds of antibiotic agents have been produced from biological compounds or chemically manufactured. Antibiotics have protected humans against different deadly bacterium attacks during the previous century. An example of a more common disease treated by antibiotics is a urinary tract infection.
One of the major concerns these days is antibiotic abuse or overuse. This is seen in cases in which medicine is being given or bought for non-installed infections and used in methods other than the intended application of the medication. These include signaling antimicrobials as a prophylactic. For example, in cancer therapy and treatment of chronic diseases such as diabetes type 2 and dental procedures, antibiotic abuse can be observed.
Moreover, antibiotics are not completely safe medicines as they may change our gut microbiota. For example, antibiotic resistance genes have recently been identified in the human microbiome, which acts as an amazing reservoir and it was found that resistant bacteria can colonize in the intestine as soon as 3 days after birth, and by choosing resistant bacteria that can behave as opportunistic pathogens, antibiotics can create some alterations in the native microbiota of the host. In addition, a low dosage consumption of sub-therapeutic antibiotic treatment or antibiotics from the environment or food resources can lead to gut dysbiosis. Furthermore, side effects of antibiotics are not limited to gut dysbiosis. For instance, antibiotic use may also lead to allergy, nephritis, hematological problems, disturbance in the nervous system, and problems with electrolytes.
To diminish some antibiotic-associated hazards, several ways have been suggested, and one of the most confident manners is use of probiotics. Probiotics are described as live microorganisms which provide health benefits to the host when applied in appropriate quantities., Lactic acid bacteria (notably Lactococcus and Lactobacillus) are two probiotic strains that have been shown to have a positive impact on human health. All of these strains have been labeled as “generally recognized as safe,” and they can be found in some foods which will be discussed in the Probiotic Food Sources section.
| Prosperities of Different Types of Probiotics|| |
Probiotics are derived from the Latin word, “pro” means “for” and the Greek word “biotic” means “life.” Bacteria-derived products, dead bacteria, metabolites, bacterial growth end products, cell wall fragments, enzymes, and neurochemicals have been proposed to have health benefits, but these are not called probiotics because they are not alive when consumed or received.,
The most common method of receiving a probiotic is orally via a number of different types including foods, pills, sachets, and tablets.,, The selection format of a probiotic can vary due to factors such as product availability, an individual’s needs or requirements, and even come down to something as simple as personal preference.,,
In addition to the properties mentioned in [Figure 1], there are other properties which should also be considered. For example, a good probiotic must be predominantly of human origin, with empirical proof of positive physiological effects and protection for human usage. It must also be willing to adhere to the target tissue properly.
In food microbiology and human nutrition, Lactobacillus species are one of the most important taxa. Several Lactobacillus species are utilized as starter cultures or food additives in the fermentation of fermented foods. This particular group of bacteria has probiotic characteristics. Add to the Lactobacillus species, Bifidobacteria species are also involved in the probiotic group [Table 1]. Bifid or irregular V- or Y-shaped rods resembling branches are the most common morphologies among these bacteria., The genus Bifidobacterium includes various organisms, some of which have been linked to health benefits such as diarrhea prevention, the establishment of a balanced microflora in premature infants, and even the prevention of gastrointestinal cancers.,, As a result of these benefits, many scholars have proposed Bifidobacteria as dietary supplements over the last century.
|Table 1: A comparison between the Bifidobacteria and Lactobacillus species|
Click here to view
| Gut Microbiota and Effects of Antibiotics|| |
Recent research has shed light on the possible effects of antibiotic use on the microbiota of the intestine. Antibiotics have been shown to reduce the variability of the gut microbiota in humans, and irritable use of antibiotics can lead to severe and inadvertent problems.,,, For example, antibiotics raise the amount of host-derived free sialic acid in the intestine, which opportunistic pathogens such as Clostridium difficile and Salmonella typhimurium may use to boost their development. Furthermore, Jakobsson et al. examined the effects of clarithromycin, omeprazole, and metronidazole on fecal taxonomic and pharyngeal composition for 7 days, and they discovered wide taxonomic contrapuntal impact, with quick but only relative recovery; in some cases, the impact lasted for about 4 years. Additionally, Dethlefsen et al. used the 16S rRNA sequencing technique and discovered that 5 days of ciprofloxacin reduced taxonomic richness and affected the diversity of around 30% of the bacterial taxa in the intestine within days of early introduction.
Antibiotics can cause dysbiosis in our gut microbiota that can lead to some diseases. For example, immune responses may be dysregulated, antibiotic-associated diarrhea (AAD) may occur, irritable bowel disease may develop, and there may even be neuropsychiatric side effects.,,,,
Additionally, another field of study about antibiotics effects on the gut microbiota is the resistance effect. For this purpose, several methods have been proposed and the most popular of which is genomic and metagenomic approach, as well as monitoring the phenotypes of specific organisms., According to Löfmark et al., up to 2 years after clindamycin application, an enrichment and stabilization of resistant bacteroides strains as well as resistance determinants can be seen. Moreover, a typical Helicobacter pylori treatment selects for highly resistant enterococci that can survive without further selection for at least 3 years.
| Probiotics Effects on Lowering Antibiotics-related Disease|| |
It has been proposed that modulating the gut microbiome may be a useful therapeutic method for reducing the harmful side effects of drugs that have a negative impact on the gut microbiota [Table 2]. For example, Koning et al. could modulate the side effects of amoxicillin by probiotic intake.
|Table 2: Effectiveness of probiotics in the treatment of diseases which can be caused by use of antibiotics|
Click here to view
In the human body, the specific mechanism of probiotics is poorly understood and is thought to work by limiting pathogenic bacteria proliferation and avoiding pathogenic penetration of the host, increasing the function of the gut wall and receptor connections, and generating or secreting substances including short-chain fatty acids and neurotransmitters.
| Probiotic Food Sources|| |
Diet has a key role on the gut microbiota and can significantly impact gut microbial richness and diversity. Dairy products including yogurts, kefirs, and cultured drinks are the main food sources for probiotic applications, and the application of probiotic bacteria in dairy products has been widely increased in the dairy industry. Furthermore, ice cream and frozen dairy treats have shown to be excellent transporters for probiotic microorganisms, because they benefit from useful features during the storage period and this leads to higher probiotic survivability at the time of consumption.
Fermented foods and beverages such as fermented milk, meat (e.g., fermented sausages), and plant‐based foods (e.g., sauerkraut) have long been consumed as an important part of the human diet in almost every culture on every continent. Regarding curing salts, spices, and other ingredients used in the formulation of the fermented sausages, selected microorganisms for these products are resistant to these ingredients as well as fermentation process. Due to the growing trend of vegetarians and the high incidence of lactose intolerance in many regions around the world, plant-based cuisines have also been introduced. Lactose intolerance, cholesterol levels, and allergic milk proteins are all important downsides of dairy consumption, necessitating the creation of new non-dairy probiotic meals.
Fruit juices are being examined as a substitute substrate for non-dairy probiotic beverages. Fruit juices provide additional benefits for the survival and growth of probiotic microbes. They are particularly high in minerals and carbohydrates, both of which are necessary for probiotic development.,
| Conclusion|| |
Antibiotics are exceptionally useful in the treatment or prevention of bacterial diseases in different creatures. However, improper use of antibiotics may lead to a wide range of inevitable hazards such as dysbiosis which is modification of gut microbiota balance. This change can lead to some further problems such as psychological disorders, IBS, diarrhea, etc. Several methods are proposed to reduce these side effects, and one of them is food-probiotic-resources consumption (such as fruit juices and dairy products), because probiotics are good substitute for lost bacteria. Additionally, their efficacy in the treatment of different antibiotic-associated side effects has been proved in several studies. For example, the incidence of AAD among patients who received probiotics for 4–16 days was absolutely lower than that of the placebo group.
The author highly thanks Mr. Josh Davidson for his help and constructive comments.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Zhang S, Chen DC, Chen LM Facing a new challenge: The adverse effects of antibiotics on gut microbiota and host immunity [Internet]. Chin Med J (Engl) 2019;132:1135-8.
Gaynes R The discovery of penicillin—New insights after more than 75 years of clinical use. Emerg Infect Dis 2017;23:849-53.
Waller TA, Pantin SAL, Yenior AL, Pujalte GGA Urinary tract infection antibiotic resistance in the United States [Internet]. Prim Care Clin Off Pract 2018;45:455-66. Available from: https://pubmed.ncbi.nlm.nih.gov/30115334/
Oberoi SS, Dhingra C, Sharma G, Sardana D Antibiotics in dental practice: How justified are we. Int Dent J 2015;65:4-10.
Cunha BA Antibiotic side effects. Med Clin North Am 2001;85:149-85.
Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, et al
. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci USA 2011;108(Suppl. 1): 4578-85.
Bezirtzoglou E, Stavropoulou E Immunology and probiotic impact of the newborn and young children intestinal microflora. Anaerobe 2011;17:369-74.
Heta S, Robo I The side effects of the most commonly used group of antibiotics in periodontal treatments. Med Sci 2018;6:6. Available from: http://www.mdpi.com/2076–3271/6/1/6
Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al
. Expert Consensus Document. The International Scientific Association for Probiotics and Prebiotics Consensus Statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11:506-14.
Lahner E, Bellisario C, Hassan C, Zullo A, Esposito G, Annibale B Probiotics in the treatment of diverticular disease. A systematic review [Internet]. J Gastrointest Liver Dis 2016;25:79-86. Available from: https://pubmed.ncbi.nlm.nih.gov/27014757/
Koirala S, Anal AK Probiotics-based foods and beverages as future foods and their overall safety and regulatory claims. Futur Foods 2021;3:100013.
Meurman JH, Stamatova I Probiotics: Contributions to oral health. Oral Dis 2007;13:443-51.
de Almada CN, Almada CN, Martinez RCR, Sant’Ana AS Paraprobiotics: Evidences on their ability to modify biological responses, inactivation methods and perspectives on their application in foods. Trends Food Sci Technol 2016;58:96-114.
Trabelsi I, Bejar W, Ayadi D, Chouayekh H, Kammoun R, Bejar S, et al
. Encapsulation in alginate and alginate coated-chitosan improved the survival of newly probiotic in oxgall and gastric juice. Int J Biol Macromol 2013;61:36-42.
Weichselbaum E Probiotics and health: A review of the evidence. Nutr Bull 2009;34:340-73. Available from: http://doi.wiley.com/10.1111/j.1467-3010.2009.01782.x
Dubey MR, Patel VP Probiotics: A promising tool for calcium absorption. Open Nutr J 2018;12:59-69.
Lin HC, Hsu CH, Chen HL, Chung MY, Hsu JF, Lien RI, et al
. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: A multicenter, randomized, controlled trial. Pediatrics 2008;122:693-700.
Siitonen S, Vapaatalo H, Salminen S, Gordin A, Saxelin M, Wikberg R, et al
. Effect of lactobacillus GG yoghurt in prevention of antibiotic associated diarrhoea. Ann Med 1990;22:57-9.
Fenster K, Freeburg B, Hollard C, Wong C, Laursen R, Ouwehand A The production and delivery of probiotics: A review of a practical approach. Microorganisms 2019;7:83.
Oyetayo VO, Oyetayo FL Potential of probiotics as biotherapeutic agents targeting the innate immune system [Internet]. Afr J Biotechnol 2005;4:123-7. Available from: http://www.academicjournals.org/AJB
Salminen S, von Wright A, Morelli L, Marteau P, Brassart D, de Vos WM, et al
. Demonstration of safety of probiotics—A review. Int J Food Microbiol 1998;44:93-106.
Goh YJ, Klaenhammer TR Genomic features of Lactobacillus
species. Front Biosci (Landmark Ed) 2009;14:1362-86.
Klijn A, Mercenier A, Arigoni F Lessons from the genomes of Bifidobacteria
[Internet]. FEMS Microbiol Rev 2005;29:491-509. Available from: https://pubmed.ncbi.nlm.nih.gov/15939502/
Lee JH, O’Sullivan DJ Genomic insights into Bifidobacteria
. Microbiol Mol Biol Rev 2010;74:378-416.
Butta H, Sardana R, Vaishya R, Singh KN, Mendiratta L Bifidobacterium
: An emerging clinically significant metronidazole-resistant anaerobe of mixed pyogenic infections. Cureus 2017;9:e1134.
Chenoll E, Casinos B, Bataller E, Astals P, Echevarría J, Iglesias JR, et al
. Novel probiotic Bifidobacterium bifidum
CECT 7366 strain active against the pathogenic bacterium Helicobacter pylori
. Appl Environ Microbiol 2011;77:1335-43.
Khailova L, Mount Patrick SK, Arganbright KM, Halpern MD, Kinouchi T, Dvorak B Bifidobacterium bifidum
reduces apoptosis in the intestinal epithelium in necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2010;299:G1118-27.
Hidalgo Cantabrana C, Delgado S, Ruiz L, Ruas-Madiedo P, Sánchez B, Margolles A Bifidobacteria and their health-promoting effects. 2018. doi:10.1128/9781555819705.ch3.
Kurman JA The health potential of products containing bifidobacteria [Internet]. 1991 [cited 2022 Feb 7]. Available from: https://ci.nii.ac.jp/naid/10027993986/
Mital BK, Garg SK Acidophilus milk products: Manufacture and therapeutics. Food Rev Int 1992;8:347-89.
Chramostová J, Mošnová R, Lisová I, Pešek E, Drbohlav J, Němečková I Influence of cultivation conditions on the growth of Lactobacillus acidophilus, Bifidobacterium sp., and Streptococcus thermophilus, and on the production of organic acids in fermented milks. Czech J Food Sci 2014;32:422-9.
Biavati B, Mattarelli P Bifidobacterium. In: Bergey’s Manual of Systematics of Archaea and Bacteria [Internet]. Wiley; 2015 [cited 2021 Mar 2]. p. 1-57. doi: 10.1002/9781118960608.gbm00019.
Salvetti E, Torriani S, Felis GE The genus Lactobacillus
: A taxonomic update. Probiotics Antimicrob Proteins 2012;4:217-26.
Ribeiro CFA, Silveira GGDOS, Cândido EDS, Cardoso MH, Espínola Carvalho CM, Franco OL Effects of antibiotic treatment on gut microbiota and how to overcome its negative impacts on human health [Internet]. ACS Infect Dis 2020;6:2544-59. Available from: https://dx.doi.org/10.1021/acsinfecdis.0c00036
Yassour M, Vatanen T, Siljander H, Hämäläinen AM, Härkönen T, Ryhänen SJ, et al
; DIABIMMUNE Study Group. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med 2016;8:343ra81.
Modi SR, Collins JJ, Relman DA Antibiotics and the gut microbiota. J Clin Invest 2014;124:4212-8.
Ng KM, Ferreyra JA, Higginbottom SK, Lynch JB, Kashyap PC, Gopinath S, et al
. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 2013;502:96-9.
Jakobsson HE, Jernberg C, Andersson AF, Sjölund-Karlsson M, Jansson JK, Engstrand L Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One 2010;5:e9836.
Dethlefsen L, Huse S, Sogin ML, Relman DA The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16s rRNA sequencing. PLoS Biol 2008;6:e280.
Amoroso C, Perillo F, Strati F, Fantini M, Caprioli F, Facciotti F The role of gut microbiota biomodulators on mucosal immunity and intestinal inflammation. 2020. doi:10.3390/cells9051234.
Strzępa A, Lobo FM, Majewska-Szczepanik M, Szczepanik M Antibiotics and autoimmune and allergy diseases: Causative factor or treatment? Int Immunopharmacol 2018;65:328-41.
Kaur N, Chen CC, Luther J, Kao JY Intestinal dysbiosis in inflammatory bowel disease. Gut Microbes 2011;2:211-6.
Bergogne-Bérézin E Treatment and prevention of antibiotic associated diarrhea. Int J Antimicrob Agents 2000;16:521-6.
Ahmed AIA, van der Heijden FMMA, van den Berkmortel H, Kramers K A man who wanted to commit suicide by hanging himself: An adverse effect of ciprofloxacin. Gen Hosp Psychiatry 2011;33:82.e5-7. Available from: https://pubmed.ncbi.nlm.nih.gov/21353135/
Löfmark S, Jernberg C, Jansson JK, Edlund C Clindamycin-induced enrichment and long-term persistence of resistant Bacteroides
spp. and resistance genes. J Antimicrob Chemother 2006;58:1160-7.
Sjölund M, Wreiber K, Andersson DI, Blaser MJ, Engstrand L Long-term persistence of resistant Enterococcus
species after antibiotics to eradicate Helicobacter pylori
. Ann Intern Med 2003;139:483-7.
Ichim TE, Kesari S, Shafer K Protection from chemotherapy- and antibiotic-mediated dysbiosis of the gut microbiota by a probiotic with digestive enzymes supplement. Oncotarget 2018;9:30919-35.
Koning CJ, Jonkers DM, Stobberingh EE, Mulder L, Rombouts FM, Stockbrügger RW The effect of a multispecies probiotic on the intestinal microbiota and bowel movements in healthy volunteers taking the antibiotic amoxycillin. Am J Gastroenterol 2008;103: 178-89.
Van Gossum A, Dewit O, Louis E, de Hertogh G, Baert F, Fontaine F, et al
. Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii
LA1) on early endoscopic recurrence of Crohn’s disease after ileo-caecal resection. Inflamm Bowel Dis 2007;13:135-42. Available from: https://pubmed.ncbi.nlm.nih.gov/17206696/
Bjarnason I, Sission G, Hayee B A randomised, double-blind, placebo-controlled trial of a multi-strain probiotic in patients with asymptomatic ulcerative colitis and Crohn’s disease. Inflammopharmacology 2019;27:465-73.
Yilmaz I, Dolar E, Ozpınar H Effect of administering kefir on the changes in fecal microbiota and symptoms of inflammatory bowel disease: A randomized controlled trial. Turkish J Gastroenterol 2018;30. doi:10.5152/tjg.2018.18227.
Preston K, Krumian R, Hattner J, de Montigny D, Stewart M, Gaddam S Lactobacillus acidophilus
CL1285, Lactobacillus casei
LBC80 and Lactobacillus rhamnosus
CLR2 improve quality-of-life and IBS symptoms: A double-blind, randomised, placebo-controlled study. Benef Microbes 2018;9:697-706.
Lewis E, Antony J, Crowley D, Piano A, Bhardwaj R, Tompkins T, Evans M Efficacy of Lactobacillus paracasei HA-196 and Bifidobacterium longum R0175 in alleviating symptoms of irritable bowel syndrome (IBS): A randomized, placebo-controlled study. Nutrients 2020;12:1159.
Ruszczyński M, Radzikowski A, Szajewska H Clinical trial: Effectiveness of Lactobacillus rhamnosus
(strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children. Aliment Pharmacol Ther 2008;28:154-61.
Esposito C, Roberti A, Turrà F, Cerulo M, Severino G, Settimi A, et al
. Frequency of antibiotic-associated diarrhea and related complications in pediatric patients who underwent hypospadias repair: A comparative study using probiotics vs placebo. Probiotics Antimicrob Proteins 2018;10:323-8.
Pinto-Sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT, et al
. Probiotic Bifidobacterium longum
NCC3001 reduces depression scores and alters brain activity: A pilot study in patients with irritable bowel syndrome. Gastroenterology 2017;153:448-59.e8.
Slykerman RF, Hood F, Wickens K, Thompson JMD, Barthow C, Murphy R, et al
; Probiotic in Pregnancy Study Group. Effect of Lactobacillus rhamnosus
HN001 in pregnancy on postpartum symptoms of depression and anxiety: A randomised double-blind placebo-controlled trial. EBioMedicine 2017;24:159-65.
Rudzki L, Ostrowska L, Pawlak D, Małus A, Pawlak K, Waszkiewicz N, et al
. Probiotic Lactobacillus plantarum
299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study. Psychoneuroendocrinology 2019;100:213-22.
Cremon C, Barbaro MR, Ventura M, Barbara G Pre- and probiotic overview [Internet]. Curr Opin Pharmacol 2018;43:87-92. Available from: https://pubmed.ncbi.nlm.nih.gov/30219638/
Granato D, Branco GF, Nazzaro F, Cruz AG, Faria JAF Functional foods and nondairy probiotic food development: Trends, concepts, and products. Compr Rev Food Sci Food Saf 2010;9:292-302.
Kandylis P, Pissaridi K, Bekatorou A, Kanellaki M, Koutinas AA Dairy and non-dairy probiotic beverages. Curr Opin Food Sci 2016;7:58-63.
Cruz AG, Antunes AEC, Sousa ALOP, Faria JAF, Saad SMI Ice-cream as a probiotic food carrier. Food Res Int 2009;42:1233-9.
Freitas RE, Pflanzer SB, Gomes CL Probiotic meat products. In: Rigobelo EC, editor. Probiotic in Animals [Internet]. London: IntechOpen; 2012 [cited 2022 Feb 07]. Available from: https://www.intechopen.com/chapters/39591
. doi: 10.5772/50057.
[Table 1], [Table 2]