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Probiotics to Prevent Antibiotic Resistance: the Time is Now

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By Kristine Koppelhus MSc Nutrition, BioGaia

What is antibiotic resistance?

Drug-resistant bacteria that have adapted and acquired the ability to survive in the presence of the drugs intended to kill them. The result is that our pool of effective drugs is shrinking as antibiotics are becoming less effective at treating diseases. Overuse and misuse of antibiotics in both humans and animals is speeding up this process. Without working antibiotics, lifesaving cancer chemotherapy or major surgeries, including organ transplants, hip replacements, but also routine interventions like appendix removal or C-sections can become life-threatening. Common infections like pneumonia, tuberculosis or gonorrhea can become incurable.

Status and threat

In 2019, the CDC reported that over 2.8 million antibiotic-resistant infections are diagnosed annually in the USA, resulting in over 35.000 deaths yearly1. Worldwide, the yearly death toll from antibiotic-resistant infections is estimated at 700.000, with 230.000 deaths attributed to multidrug-resistant tuberculosis2. In newborns specifically, global estimates say that 214,000 deaths each year are attributable to sepsis caused by antibiotic-resistant pathogens3. Although many countries have made significant efforts in the past decade to slow down antimicrobial resistance, it is a serious and urgent global issue that requires significant, immediate action. In its 2019 report, the United Nations’ Interagency Coordination Group on antimicrobial resistance estimates that the prevalence of antibiotic resistant infections could rise to 10 million a year by 2050 if no action is taken2.

Call for action

The key message from all expert bodies is that drug-resistant infections are not a future threat or a “somewhere else” threat that can be taken lightly. We all know very well how microbes and pathogens can spread easily across the globe. Antimicrobial resistance is spreading right now, and we are exhausting our treatment options for several infections of public health concern. Considering that no new antimicrobial classes have been discovered since the late 1980s4, the best course of action is to protect the efficacy of those that we already have. But how? As, stipulated in the WHO global action plan from 2015 the way forward requires a whole-of-society engagement including a One Health approach with a prevention first mindset towards reducing antibiotics overuse and misuse: every infection prevented is one that needs no antibiotics. It also requires equitable access to and appropriate use of antimicrobial medicines globally and the implementation of national action plans5.

A preventive approach to reduce antibiotics use

In the fight against resistance, we, in line with WHO5 advocate for an increased focus on prevention along with other initiatives that can slow down and control the development of resistance. We need to decrease overuse and misuse of antibiotics right now and we need to adopt a long-term approach to preventing infectious diseases and the spread of infections in general.

In addition to promoting the proper usage of antibiotics (antibiotic stewardship), a preventive approach could involve the use of Probiotics. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host6. A 2015 systematic Cochrane review stated that Probiotics significantly reduced the episodes of acute upper respiratory tract infections, the mean duration of infection, antibiotic use and school absence7. Results were later confirmed in another systematic review by King and colleagues (2019) showing that infants and children given probiotics had a reduced risk of both acute respiratory tract infections and acute lower digestive tract infections. Importantly, this review also found that probiotics use may be associated with a reduced antibiotic use8.

This benefit of preventive use of probiotics was supported by another analysis by Lenoir-Wijnkoop et al. (2019) in a US primary care setting9. Their analysis, based on data from 2017-2018, highlighted a positive impact of probiotics on the health care and economic burden of flu-like respiratory tract infections. Improved disease outcomes translated into considerable cost savings for both the payer and society. More specifically, their analysis showed that generalized probiotic intake in the US population estimated for 2017–2018 would have allowed cost savings between 4 and 370 million USD and would have averted between 1.4–2.2 million courses of antibiotic prescriptions9.

The next challenge of microbiome research

The human gut microbiome (i.e., the community of resident gut bacteria and their genes), is acquired early in life. The microbiome can be a reservoir of potential antibiotic resistance genes that could be transferred to pathogenic microbes under permissive circumstances (e.g., unnecessary use of antibiotics)10. Studies have shown that probiotic supplementation in early life can modify the gut microbiome to reduce the number of antibiotic resistant genes in the bacteria transferred from the mother to the infant11. In adults, the effects of targeted probiotic intervention can recapitulate the decrease in antibiotic resistance gene abundance in some people but not in others; research is ongoing to better understand the relationship between an individual’s microbiome, antibiotics, and probiotics and how each individual microbiome allows or opposes the action of specific probiotics.

During the past 1.5 year the COVID-19 pandemic has affected our lives in ways we never could have imagined. In the wait for vaccines, preventive strategies using probiotics were suggested9 and the first studies on the potential impact of probiotics on management of COVID-19 emerged10 and more will come in the aftermath of the pandemic. The potential mode of action of probiotics and probiotic-derived factors in enhancing health and regulating host homeostasis and immune health are discussed12,13,14,15. It will be exciting to better understand the role probiotics have in strengthening of the immune defense, gut homeostasis and in the gut-brain and gut-lung interactions.

Scientists have spent decades investigating the many good microbes that inhabit our intestinal tracts leading to a much greater understanding of what they do and how they work. Many advances were made, yet a lot is left to understand. We need more cross-disciplinary research to understand which interventions are effective for whom and how precision targeting might be implemented in a larger scale to achieve the necessary goals.

So, what can I do here and now to help?

You can help spread awareness by joining the World Antimicrobial Awareness Week (WAAW) celebrated between 18-24 November each year.  Aiming to increase awareness of global antimicrobial resistance (AMR) and to encourage best practices among the general public, health workers, farmers, animal health professionals and policy makers to avoid the further emergence and spread of drug-resistant infections. The campaign is supported by the World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO) and the World Organization for Animal Health (OIE). The Tripartite Organizations are happy to share their AMR- and WAAW-related advocacy and communications materials for use and distribution. Infographics:

More details about the campaign

References

  1. CDC. Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019 https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf
  2. No time to wait: securing the future from drug-resistant infections. Report to the secretary-general of the United Nations. April 2019 https://www.who.int/docs/default-source/documents/no-time-to-wait-securing-the-future-from-drug-resistant-infections-en.pdfsfvrsn=5b424d7_6
  3. Laxminarayan R, Matsoso P, Pant S, Brower C, Røttingen JA, Klugman K, Davies S. Access to effective antimicrobials: a worldwide challenge. Lancet. 2016 Jan 9;387(10014):168-75. doi: 10.1016/S0140-6736(15)00474-2.
  4. Why big pharma has abandoned antibiotics https://www.nature.com/articles/d41586-020-02884-3
  5. Global action plan on antimicrobial resistance, 2015. https://www.who.int/publications/i/item/9789241509763
  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.doi: 10.1038/nrgastro.2014.66
  7. Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015 Feb 3;(2):CD006895. doi: 10.1002/14651858.CD006895.pub3. PMID: 25927096.
  8. King S, Tancredi D, Lenoir-Wijnkoop I, Gould K, Vann H, Connors G, Sanders ME, Linder JA, Shane AL, Merenstein D. Does probiotic consumption reduce antibiotic utilization for common acute infections? A systematic review and meta-analysis. Eur J Public Health. 2019 Jun 1;29(3):494-499. doi: 10.1093/eurpub/cky185. PMID: 30219897; PMCID: PMC6532828.
  9. Lenoir-Wijnkoop I, Merenstein D, Korchagina D, Broholm C, Sanders ME, Tancredi D. Probiotics Reduce Health Care Cost and Societal Impact of Flu-Like Respiratory Tract Infections in the USA: An Economic Modeling Study. Front Pharmacol. 2019 Aug 28;10:980. doi: 10.3389/fphar.2019.00980. Erratum in: Front Pharmacol. 2019 Oct 11;10:1182. PMID: 31555138; PMCID: PMC6722238.
  10. Sophie A Baron, Seydina M Diene, Jean-Marc Rolain, Human microbiomes and antibiotic resistance, Human Microbiome Journal, Volume 10, 2018, Pages 43-52, https://www.sciencedirect.com/science/article/pii/S2452231718300058
  11. Casaburi G, Duar RM, Vance DP, Mitchell R, Contreras L, Frese SA, Smilowitz JT, Underwood MA. Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria. Antimicrob Resist Infect Control. 2019 Aug 14;8:131. doi: 10.1186/s13756-019-0583-6. PMID: 31423298; PMCID: PMC6693174.
  12. Baud D, Dimopoulou Agri V, Gibson GR, Reid G, Giannoni E. Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic. Front Public Health. 2020 May 8;8:186. doi: 10.3389/fpubh.2020.00186. PMID: 32574290; PMCID: PMC7227397.
  13. d’Ettorre G, Ceccarelli G, Marazzato M, Campagna G, Pinacchio C, Alessandri F, Ruberto F, Rossi G, Celani L, Scagnolari C, Mastropietro C, Trinchieri V, Recchia GE, Mauro V, Antonelli G, Pugliese F, Mastroianni CM. Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19. Front Med (Lausanne). 2020 Jul 7;7:389. doi: 10.3389/fmed.2020.00389. PMID: 32733907; PMCID: PMC7358304.
  14. Sundararaman A, Ray M, Ravindra PV, Halami PM. Role of probiotics to combat viral infections with emphasis on COVID-19. Appl Microbiol Biotechnol. 2020 Oct;104(19):8089-8104. doi: 10.1007/s00253-020-10832-4. Epub 2020 Aug 19. PMID: 32813065; PMCID: PMC7434852.
  15. Olaimat AN, Aolymat I, Al-Holy M, Ayyash M, Abu Ghoush M, Al-Nabulsi AA, Osaili T, Apostolopoulos V, Liu SQ, Shah NP. The potential application of probiotics and prebiotics for the prevention and treatment of COVID-19. NPJ Sci Food. 2020 Oct 5;4:17. doi: 10.1038/s41538-020-00078-9. PMID: 33083549; PMCID: PMC7536434.

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