The role the gut microbiome has in modifying our innate immunity for better or worse infection outcomes is one of the least appreciated factors of epidemiology, likely because there isn’t much money to be made here. When salience is a function of corporate profitability modifiable risks like metabolic disease and vitamin D serum levels get ignored while patentable quick fixes get steered to the forefront of national discourse. That is why I will continue to highlight and summarize the scientific evidence for holistic alternatives and lower cost off label solutions to those being peddled by Big Pharma and their academic and regulatory stooges. Since 70-80% of the immune system is in the gut and SARS-Cov-2 has been associated with digestive system disturbances, reduced biodiversity of the gut microbiome and has been found in stool samples taken from hospitalized COVID-19 patients indicating infection in the intestines. As Hunter, Gibson and Walton mention in the British Journal of Nutrition, the angiotensin-converting enzyme 2 receptors are mostly found in the epithelium cells of the gut and one symbiotic bacteria in particular, Coprobacillus spp., up regulates the angiotensin-converting enzyme 2 which is down regulated during SARS-Coronavirus infection. The angiotensin-converting enzyme 2 itself indirectly controls the intestinal uptake of tryptophan through amino acid transporters.

A systematic review of original studies examining the impact of Bifidobacterium abundance in the gut microbiome on COVID-19 disease outcomes across the world (n = 25) found, among observational studies (n = 18), that COVID-19 is associated with a decrease in Bifidobacterium abundance while a higher prevalence of Bifidobacterium in stool and saliva samples was associated with a reduced risk of severe COVID-19 including significantly lower ICU admissions. One species in particular, Bifidobacterium bifidum, had a statistically significant inverse association with COVID-19 disease severity, after adjusting for antibiotic use and advanced age, while others such as Bifidobacterium pseudocatenulatum and Bifidobacterium adolescenteis had an inverse but non-significant association with COVID-19 disease severity. Bifidobacterium pseudocatenulatum was negatively correlated with Post Acute COVID-19 Syndrome symptoms among long COVID patients at 6 months post infection.

Among clinical trials (n = 7), all but one found beneficial effects for pro-biotic treatment of COVID-19 patients. Treatment of hospitalized COVID-19 patients with Bifidobacterium BB-12 cut average hospital stays in half and reduced mortality 4x. Treatment with three-strain probiotic consisting of Bifidobacterium lactis, Lactobacillus salivarius, and Lactobacillus acidophilus reduced C-reactive protein after 3-5 days, reduced average hospital stay by 5 days and eliminated the need for oxygen support compared to the control group. Treatment with a probiotic mix containing Streptococcus thermophilus, Lacticaseibacillus acidophilus, Lacticaseibacillus helveticus, Lacticaseibacillus paracasei, Lacticaseibacillus plantarum, Lacticaseibacillus brevis, and Bifidobacterium lactis resolved diarrhea for 93% of treated patients within 3 days and reduced the risk of respiratory failure requiring by 8x after 7 days compared to the control group. A retrospective cohort study of COVID-19 patients, with severe pneumonia, receiving the best available therapy alone or in combination with bacteriotherapy found that the bacteriotherapy combination comparatively reduced COVID-19 mortality but not ICU admission or ICU stay. Another retrospective study of severe COVID-19 patients (n = 311) found that patients who received a probiotic mix containing Bifidobacterium infantis, Lactobacillus acidophilus, Dung enterococcus, Bacillus cereus, Bifidobacterium longum, Lactobacillus bulgaricus, Streptococcus thermophilus, Bacillus subtilis had lower C-reactive protein levels and upregulated natural killer cells, B and T cells compared to the standard of care patients. Treatment with a probiotic mix containing 4 species of Lactobacilli and 3 species of Bifidobacteria for patients discharged after COVID-19 hospitalization significantly reduced inflammatory cytokine levels compared to baseline.