Potential Benefits of Probiotics in Obese COVID-19 Patients
Over the past couple of months amidst an aggressive second wave, the coronavirus disease-19 (COVID-19) pandemic has continued to emerge as an enormous burden on national public health resources, affecting and threatening even the middle-aged population this time.(1)
It has been observed that overweight or obese population are at an independent risk for development of upper and lower respiratory tract infections and delayed recovery through it.(2) Along the same lines, it is reported that obese patients carry a higher risk of contracting COVID-19 infections and developing more severe disease, including increased mortality.(3) The evidence supporting the use of probiotics in this patient population is reviewed and summarised with clinical relevance.
Effect of Probiotics on Respiratory Tract Symptoms in Obese Population: PROMAGEN study revisited
About the Study: The study aimed at assessing the impact of probiotics among overweight and obese healthy adult population.(4) The trial was qualitatively designed as a double-blind, single-centered, placebo-controlled trial. The subjects recruited included 220 adults, aged between 30-65 years, with body mass index (BMI) 25–34.9 kg/m2.(2) The participants were randomized to receive either multi-strain* Lactobacillus and Bifidobacterium based probiotic supplementation or a matched placebo daily for 6 months.
Results- Analysis of Respiratory Tract Symptoms: At the end of the study, apart from significant improvement in lipid and metabolic parameters, it was observed that there were significant differences in the respiratory symptoms between the two groups which were further analyzed.
Five key symptomatic indicators of upper respiratory tract infections (URTIs) were selected and recorded. These comprised of cough, sore throat, headache, muscle ache, and wheeze. It was demonstrated that a significant 27% self-reported between-group difference in overall incidence of respiratory symptoms supporting the probiotic group (95% confidence intervals (CI), p< 0.0001). The occurrence of cough was reduced by about 33% (p= 0.0073) in participants receiving probiotics compared to placebo.
Probiotics benefit respiratory symptoms in obese population: Further analysis using the Poisson regression model, significant interactions were noted with probiotic supplementation treatment between URTI symptom incidence, age (p= 0.0071), and BMI (p = 0.0393). On stratification of the cohort, it was identified that probiotic group had a greater impact on incidence rates of URTI symptoms in participants ≥45 years old compared to younger participants, and in obese participants compared to those overweight alone. Further analysis of additional recorded symptoms of potential relevance to URTIs (e.g., sneezing) demonstrated reduced rates of occurrence in participants taking probiotics compared to those taking placebo. Notably, a pattern was once again observed reporting benefits being generally more prominent in participants aged ≥45 years and BMI ≥30 kg/m2
Probiotics Lead to Rapid Respiratory Symptom Relief in High-Risk Population: On exploring the dynamics of onset of URTI symptoms at baseline, participants in both treatment arms were virtually symptom-free, with only one participant in the ≥45 years old placebo group reporting cough. After just 1 to 2 weeks of probiotics supplementation, there was a clear indication of divergence between groups in the time taken to record the first symptom favoring the probiotic arm; again in the two subgroups, i.e. ≥45 years and obese, suggestive of a rapid impact of the probiotic treatment on URTI symptoms. These findings in symptom onset were maintained over the complete 6-month duration of the study in both subgroups. Collectively, these findings concluded that probiotics could act rapidly, particularly in the 'at-risk' groups of older and obese participants
Key Insights from the Study & Way Forward
√ The evidence supporting the concept that gut commensal bacteria, including those commonly included in probiotics, can suppress viruses that enter the host via the upper respiratory tract from causing viral infections is growing(5).
√ Probiotic bacteria can suppress viral infections directly by absorptive trapping,(6).as well as by the production of lipopolysaccharide that binds to and destabilizes the viral structure.(7)
√ The physiological route through which probiotic bacteria may translocate from gut to the lung and undertake direct protective function is described by the 'gut-lymph hypothesis', i.e. gut bacteria within draining chyle from the lower gastrointestinal tract entering the lymphatic system and subsequently the thoracic duct, before traveling directly on to the capillary blood vessels of the lungs(8)
√ Based on available evidence, it seems that the use of probiotics has a positive impact on viral URTIs, by reducing symptoms in overweight and obese people, as well as elderly.
√ Probiotic supplementation may also have a potential role in preventing changes in gut microbiome composition in response to viral infections.
√ While the country continues to bear the brunt of second wave of the pandemic and mass vaccination programmes are still some time away, we are in times where effective and safe oral agents to manage COVID-19, even as adjuvant options in out-patient settings are valuable considerations
√ Probiotics – widely established immunomodulators are considered safe and well-tolerated. While a compelling case exists for further randomized studies to prospectively explore the potential impact of probiotics on the prevention of respiratory infection, in particular for those at higher risk, including obese, elderly suffering from COVID-19, the scientific rationale and current evidence make their consideration clinically relevant.
*Probiotic comprised Lactobacillus acidophilus CUL60 (NCIMB 30157), Lactobacillus acidophilus CUL21 (NCIMB 30156), Lactobacillus plantarum CUL66 (NCIMB 30280) Bifidobacterium bifidum CUL20 (NCIMB 30153), and Bifidobacterium animalis subsp. Lactis CUL34 (NCIMB 30172)
References
Adapted from:
1. Sundararaman A, Ray M, Ravindra PV, Halami PM. Role of probiotics to combat viral infections with emphasis on COVID-19 [published online ahead of print, 2020 Aug 19]. Appl Microbiol Biotechnol. 2020;1-16. doi:10.1007/s00253-020-10832-4
2. Maccioni L, Weber S, Elgizouli M, Stoehlker AS, Geist I, Peter HH, Vach W, Nieters A. Obesity and risk of respiratory tract infections: results of an infection-diary based cohort study. BMC Public Health. 2018;18(1):271. doi:10.1186/s12889-018-5172-8.
3. Popkin BM, Du S, Green WD, Beck MA, Algaith T, Herbst CH, Alsukait RF, Alluhidan M , Alazemi N, Shekar M. Individuals with obesity and COVID-19: a global perspective on the epidemiology and biological relationships. In: Obesity Reviews. 2020. p. 21.
4. Michael DR, Jack AA, Masetti G, Davies TS, Loxley KE, Kerry-Smith J, Plummer JF, Marchesi JR, Mullish BH, McDonald JAK, et al. A randomised controlled study shows supplementation of overweight and obese adults with lactobacilli and bifidobacteria reduces bodyweight and improves well-being. Sci Rep. 2020;10(1):4183. doi:10.1038/s41598-020-60991-7
5. Mullish BH, Marchesi JR, McDonald JAK, Pass DA, Masetti G, Michael DR, Plummer S, Jack AA, Davies TS, Hughes TR, Wang D. Probiotics reduce self-reported symptoms of upper respiratory tract infection in overweight and obese adults: should we be considering probiotics during viral pandemics? Gut Microbes. 2021 Jan-Dec;13(1):1-9. doi: 10.1080/19490976.2021.1900997. PMID: 33764850; PMCID: PMC8007143.
6. Wang Z, Chai W, Burwinkel M, Twardziok S, Wrede P, Palissa C, Esch B, Schmidt MFG. Inhibitory influence of Enterococcus faecium on the propagation of swine influenza A virus in vitro. PLoS One. 2013;8(1): e53043. doi:10.1371/journal.pone.0053043.
7. Bandoro C, Runstadler JA. Bacterial Lipopolysaccharide destabilizes influenza viruses. mSphere. 2017;2(5):2. doi:10.1128/mSphere.00267-17.
8. Deitch EA. Gut-origin sepsis: evolution of a concept. Surgeon. 2012;10(6):350–356. doi:10.1016/j. surge.2012.03.003.
Prof. Dr. T. P. Kalaniti is the Director - Medical Education, KMCH Institute of Health Sciences and Research, Coimbatore
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