ObjectiveThe study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls.DesignUsing a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels.ResultsCompared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (p<0.0001), Faecalibacterium (p=0.0077) and Roseburium (p=0.0327), while having increased Bacteroides (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria.ConclusionWe hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention.Trial registration numberNCT04031469 (PCR−) and 04359836 (PCR+).

COVID-19 is a viral pandemic that primarily manifests with respiratory distress but may also lead to symptoms and signs associated with the gastrointestinal tract. It is characteristically associated with a hyper-immune response, also referred to as a ‘cytokine storm’. Probiotics are living microorganisms that have been shown to have positive effects on immune response in man with some bacteria; some strains of Bifidobacteria, for example, possess especially potent immune modulating effects. These bacteria have the potential to ameliorate the ‘cytokine storm’ through a differential effect on pro- and anti-inflammatory cytokines. In the management of COVID-19 and other coronovirus-mediated illnesses, probiotic bacteria also have the potential to enhance vaccine efficacy.

Oral booster-single strain probiotic bifidobacteria could be a potential strategy for SARS-CoV-2. This study aims to evaluate the role of oral probiotic Bifidobacterium on moderate/severe SARS-CoV-2 inpatients. In this single-center study, we analyzed data of 44 moderate/severe inpatients with diagnosed COVID-19 in Istanbul Maltepe University Medical Faculty Hospital, 2020 from 1 November 2020 to 15 December 2020. Clinical and medication features were compared and analyzed between patients with or without probiotic. In result, 19 of the 44 patients (43.18%) who were administrated with oral booster-single strain probiotic were discharged with the median inpatient day of 7.6 days which were significantly shorter than those of patients without probiotic. There were significant differences in inpatient days, radiological improvement at day 6 and week 3, and reduction in interleukin-6 levels in those receiving oral probiotic therapy. Although the mortality rate was 5% in the probiotic group, it was 25% in the non-probiotic group. Booster-single strain probiotic bifidobacteria could be an effective treatment strategy for moderate/severe SARS-CoV-2 inpatients to reduce the mortality and length of stay in hospital.

Ulcerative colitis (UC) pathogenesis includes the altered gut microbiota, environmental factors, and human immune and genetic predisposition. Recently, its association with reduced bifidobacteria quantity in the microbiota is reported. Xyloglucan, a plant-based prebiotic oligosaccharide, causes increase in bifidobacteria quantity. In this article, we share the results of our UC cases treated by intracolonic single-dose administration of Bifidobacterium animalis subsp. lactis and xyloglucan combination. Intracolonic single-dose administration of 200 billion colony-forming units (CFUs) of B. animalis subsp. lactis and 4 g of xyloglucan combination was administrated to 10 severe UC patients, who were either unresponsive or had inadequate response to treatment. All patients continued treatment after the procedure. Treatment responses were evaluated by colonoscopic, laboratory, and clinical examination after 6 weeks. Intracolonic single-dose administration of B. animalis subsp. lactis and xyloglucan was found effective in the mucosal healing and resolution of colonic symptoms in UC patients. Intracolonic administration of B. animalis subsp. lactis and xyloglucan in UC is a new single-strain and strain-specific prebiotic combination method. It is easy to apply and has no observable side effect. Its effectiveness on mucosal healing could be attributed to the enhancement of non-stimulatory status and biodiversity in colonic mucosa. Nonetheless, it is still necessary to develop diagnostic strategies to determine the patients to whom this method would be the most applicable.

Colorectal cancer is the most preventable form of cancer worldwide. The pathogenesis of colorectal cancer includes gut inflammation, genetic and microbial composition factors. İmpairment of the gut microbiota has been associated with development of colorectal cancer. The genus Bifidobacterium is an important component of the commensal gut microbiota. Bifidobacteria are considered to have important roles in multiple homeostatic functions: immunologic, hormonal and metabolic. Mucosal-associated invariant T cells (MAIT) are components of the immune system involved in protection against infectious pathogens and regulate the pathogenesis of various inflammatory diseases and, potentially, colorectal cancer. Engagement between Bifidobacterium and MAIT cells could exert a beneficial effect on colorectal cancer prevention and treatment.

Objective: To compare gut microbiome diversity and composition in SARS-CoV-2 polymerase chain reaction (PCR)-confirmed positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls. Design: Using a cross-sectional study design, we used shotgun next-generation sequencing (NGS) to evaluate microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections presenting to Ventura Clinical Trials for care from March 2020 through January 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate, or severe symptoms based on NIH criteria.1 Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, e.g. household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls and across patient subgroups at all taxonomic levels. Results: There were 52 patients and 20 controls. Compared with controls, patients had significantly less bacterial diversity, a lower abundance of Bifidobacterium and Faecalibacterium as well as some other bacteria, and a higher abundance of Bacteroides at the genus level. Additionally, there was an inverse association between disease severity and both bacterial diversity and Bifidobacterium and Faecalibacterium abundance. Conclusion: We hypothesize that low bacterial diversity and depletion of Bifidobacterium and Faecalibacterium genera either before or after infection led to reduced pro-immune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for severe symptoms from SARS-CoV-2 infection and may be amenable to pre-, intra-, or post infection intervention.

Colorectal cancer is the third most common cancer and the third leading cause of cancer-related death. The pathogensesis of colorectal cancer involves a multi-step and multi-factorial process. Disruption of the gut microbiota has been associated with gastrointestinal diseases such as colorectal cancer. The genus Bifidobacterium is considered an important component of the commensal microbiota and plays important roles in several homeostatic functions: immune, neurohormonal, and metabolic. Bifidobacterium animalis subsp. lactis is a well-documented probiotic within the species Bifidobacterium. Mycosporin-like amino acids are low molecular weight amino acids demonstrated to exert prebiotic effects and to modulate host immunity by regulating the proliferation and differentiation of intestinal epithelial cells, macrophages and lymphocytes, as well as cytokine production.Their modulation of the metabolism of the immune system and transcription factors could exert a beneficial effect on colorectal cancer. B. animalis does not produce mycosporin-like amino acids. If one could create a B. animalis–producing mycosporin-like amino acids via genetic open reading frame engineering it should exert more potent immuno-stimulatory properties and, thereby, become a potent strain-specific microbial based therapy in colorectal cancer prevention.

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