The Role of Probiotics and Their Metabolites in the Treatment of Depression.

Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut-brain axis. While this microbiota-gut-brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota-gut-brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut-brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks.

Ecology and Machine Learning-Based Classification Models of Gut Microbiota and Inflammatory Markers May Evaluate the Effects of Probiotic Supplementation in Patients Recently Recovered from COVID-19.

Gut microbiota (GM) modulation can be investigated as possible solution to enhance recovery after COVID-19. An open-label, single-center, single-arm, pilot, interventional study was performed by enrolling twenty patients recently recovered from COVID-19 to investigate the role of a mixed probiotic, containing Lactobacilli, Bifidobacteria and Streptococcus thermophilus, on gastrointestinal symptoms, local and systemic inflammation, intestinal barrier integrity and GM profile. Gastrointestinal Symptom Rating Scale, cytokines, inflammatory, gut permeability, and integrity markers were evaluated before (T0) and after 8 weeks (T1) of probiotic supplementation. GM profiling was based on 16S-rRNA targeted-metagenomics and QIIME 2.0, LEfSe and PICRUSt computational algorithms. Multiple machine learning (ML) models were trained to classify GM at T0 and T1. A statistically significant reduction of IL-6 (p < 0.001), TNF-α (p < 0.001) and IL-12RA (p < 0.02), citrulline (p value < 0.001) was reported at T1. GM global distribution and microbial biomarkers strictly reflected probiotic composition, with a general increase in Bifidobacteria at T1. Twelve unique KEGG orthologs were associated only to T0, including tetracycline resistance cassettes. ML classified the GM at T1 with 100% score at phylum level. Bifidobacteriaceae and Bifidobacterium spp. inversely correlated to reduction of citrulline and inflammatory cytokines. Probiotic supplementation during post-COVID-19 may trigger anti-inflammatory effects though Bifidobacteria and related-metabolism enhancement.

Effect of probiotics as an immune modulator for the management of COVID-19.

COVID-19, an acute respiratory viral infection conveyed by pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of individuals globally, and is a public health emergency of international concern. Till now, there are no highly effective therapies for this infection without vaccination. As they can evolve quickly and cross the strain level easily, these viruses are causing epidemics or pandemics that are allied with more severe clinical diseases. A new approach is needed to improve immunity to confirm the protection against emerging viral infections. Probiotics can modify gut microbial dysbiosis, improve the host immune system, and stimulate immune signaling, increasing systemic immunity. Several probiotic bacterial therapies have been proven to decrease the period of bacterial or viral infections. Superinduction of inflammation, termed cytokine storm, has been directly linked with pneumonia and severe complications of viral respiratory infections. In this case, probiotics as potential immunomodulatory agents can be an appropriate candidate to improve the host's response to respiratory viral infections. During this COVID-19 pandemic, any approach that can induce mucosal and systemic immunity could be helpful. Here, we summarize contexts regarding the effectiveness of various probiotics for preventing virus-induced respiratory infectious diseases, especially those that could be employed for COVID-19 patients. In addition, the effects of probiotics, their mechanisms on different aspects of immune responses against respiratory viral infection, and their antiviral properties in clinical findings have been described in detail.

Gut microbiome therapeutic modulation to alleviate drug-induced hepatic damage in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) infection caused by the severe acute respiratory syndrome coronavirus 2 virus, its symptoms, treatment, and post-COVID-19 effects have been a major focus of research since 2020. In addition to respiratory symptoms, different clinical variants of the virus have been associated with dynamic symptoms and multiorgan diseases, including liver abnormalities. The release of cytokines by the activation of innate immune cells during viral infection and the high doses of drugs used for COVID-19 treatment are considered major drivers of liver injury in COVID-19 patients. The degree of hepatic inflammation in patients suffering from chronic liver disease and having COVID-19 could be severe and can be estimated through different liver chemistry abnormality markers. Gut microbiota influences liver chemistry through its metabolites. Gut dysbiosis during COVID-19 treatment can promote liver inflammation. Here, we highlighted the bidirectional association of liver physiology and gut microbiota (gut-liver axis) and its potential to manipulate drug-induced chemical abnormalities in the livers of COVID-19 patients.

Multistrain Probiotics Supplement Alleviates Asthma Symptoms via Increasing Treg Cells Population: A Randomized, Double-Blind, Placebo-Controlled Trial.

INTRODUCTION: The favorable effects of probiotics have been demonstrated in allergic disorders. However, the underlying immunological mechanisms are poorly understood. In the present study, we investigated the improvement of clinical symptoms and immunological balance after receiving probiotics in patients with asthma. METHODS: The present study was a randomized, double-blind, placebo-controlled trial in which 40 patients with asthma were enrolled. They were treated with probiotics or placebo: 1 capsule/day for 8 weeks. Pulmonary function test, percentage of CD4+ CD25+ FoxP3+ Tregs, and gene expression of T-bet, GATA-3, RORγt, and Foxp3 in PBMCs were assessed at baseline and after treatment. RESULTS: Our results showed a significant increase in the expression of FoxP3 and CD4+ CD25+ FoxP3+ Tregs population, while RORγt and GATA3 expression were reduced. In addition, pulmonary function tests showed a significant improvement in forced expiratory volume and forced vital capacity after receiving probiotics. DISCUSSION/CONCLUSION: Our findings demonstrate that 8-week treatment with probiotic supplementation can control T-helper 2-predominant and Th17 pro-inflammatory responses and improve forced vital and forced expiratory volume in asthmatic patients. It seems probiotics can be used besides common treatments for patients with asthma.

Potential Use of a Combined Bacteriophage-Probiotic Sanitation System to Control Microbial Contamination and AMR in Healthcare Settings: A Pre-Post Intervention Study.

Microbial contamination in the hospital environment is a major concern for public health, since it significantly contributes to the onset of healthcare-associated infections (HAIs), which are further complicated by the alarming level of antimicrobial resistance (AMR) of HAI-associated pathogens. Chemical disinfection to control bioburden has a temporary effect and can favor the selection of resistant pathogens, as observed during the COVID-19 pandemic. Instead, probiotic-based sanitation (probiotic cleaning hygiene system, PCHS) was reported to stably abate pathogens, AMR, and HAIs. PCHS action is not rapid nor specific, being based on competitive exclusion, but the addition of lytic bacteriophages that quickly and specifically kill selected bacteria was shown to improve PCHS effectiveness. This study aimed to investigate the effect of such combined probiotic-phage sanitation (PCHSφ) in two Italian hospitals, targeting staphylococcal contamination. The results showed that PCHSφ could provide a significantly higher removal of staphylococci, including resistant strains, compared with disinfectants (-76%, p < 0.05) and PCHS alone (-50%, p < 0.05). Extraordinary sporadic chlorine disinfection appeared compatible with PCHSφ, while frequent routine chlorine usage inactivated the probiotic/phage components, preventing PCHSφ action. The collected data highlight the potential of a biological sanitation for better control of the infectious risk in healthcare facilities, without worsening pollution and AMR concerns.

Gut microbiota in COVID-19: new insights from inside.

The epidemic of coronavirus disease-19 (COVID-19) has grown to be a global health threat. Gastrointestinal symptoms are thought to be common clinical manifestations apart from a series of originally found respiratory symptoms. The human gut harbors trillions of microorganisms that are indispensable for complex physiological processes and homeostasis. Growing evidence demonstrate that gut microbiota alteration is associated with COVID-19 progress and severity, and post-COVID-19 syndrome, characterized by decrease of anti-inflammatory bacteria like Bifidobacterium and Faecalibacterium and enrichment of inflammation-associated microbiota including Streptococcus and Actinomyces. Therapeutic strategies such as diet, probiotics/prebiotics, herb, and fecal microbiota transplantation have shown positive effects on relieving clinical symptoms. In this article, we provide and summarize the recent evidence about the gut microbiota and their metabolites alterations during and after COVID-19 infection and focus on potential therapeutic strategies targeting gut microbiota. Understanding the connections between intestinal microbiota and COVID-19 would provide new insights into COVID-19 management in the future.

Probiotics and COVID-19: is there any link?

Understanding mechanisms of the novel SARS-CoV2 infection and progression can provide potential novel targets for prevention and/or treatment. This could be achieved via the inhibition of viral entry and/or replication, or by suppression of the immunologic response that is provoked by the infection (known as the cytokine storm). Probiotics are defined as 'live microorganisms that, when administered in adequate amounts, confer a health benefit on the host'. There is scarcity of evidence about the relationship between COVID-19 and gut microbiota. So, whether or not these supplements can prevent or ameliorate COVID-19-associated symptoms is not fully understood. The aim of this study is to provide an indirect evidence about the utility of probiotics in combating COVID-19 or its associated symptoms, through the review of its antiviral and anti-inflammatory properties in vitro, animal models and human trials. SIGNIFICANCE AND IMPACT OF THE STUDY: The role of probiotics in alleviation of the novel COVID-19 has not been established. This review provides an insight about the anti-inflammatory, antiviral effects of probiotics in vitro, animal models and human. The latter can provide an indirect evidence and/or hypothesis-driven approach to investigate the use of probiotics as adjunctive therapy in the prophylaxis and/or alleviation of COVID-19 symptoms.

COVID-19, the Gut, and Nutritional Implications.

PURPOSE OF REVIEW: Our goal is to provide the most recent and accurate scientific evidence available regarding COVID-19's interaction with the human gut and the role of nutrition/nutritional supplementation in the prevention and treatment of the disease. RECENT FINDINGS: Gastrointestinal symptoms of COVID-19 are common and often persist even after classically defined illness resolution. Nutritional status and content have been shown to impact infection risk and severity. Well-balanced diets are associated with decreased infection risk/severity, and early nutrition is associated with better outcomes in the critically ill. No specific vitamin supplementation regimen has shown consistent benefit for infection treatment or prevention. The impact of COVID-19 extends far past the pulmonary system, and its impact on the gut should not be ignored. For those interested in adopting lifestyle modifications to prevent severe COVID-19 infection/side effects, consideration should be made for adoption of a well-balanced diet (e.g., Mediterranean style), utilization of probiotics, and addressing nutritional/vitamin deficiencies. Future, high-quality research is needed in this arena.

[Efficacy of Saccharomyces boulardii CNCM I-745 probiotic drug in the prevention and treatment of diarrhea in hospitalized patients with new coronavirus infection COVID-19].

AIM: To evaluate the efficacy of Saccharomyces boulardii (S. boulardii) CNCM I-745 probiotic drug in preventing and treating diarrhea in hospitalized patients with COVID-19. MATERIALS AND METHODS: A prospective comparative study was conducted in two parallel groups. The study included males and females aged 18 to 60 with the following diagnosis confirmed by polymerase chain reaction: U07.2 Coronavirus infection COVID-19, caused by SARS-CoV-2 virus (grade 1-3 pneumonia according to CT scan). All patients received antibiotic therapy. The patients were subdivided into two equal groups (n=60) depending on the administration of S. boulardii CNCM I-745 probiotic drug in addition to standard treatment. The probiotic was prescribed by the attending physician; the dose was 2 capsules per day (500 mg/day) 30 min before the meal for 10 days. All patients were monitored for main clinical, laboratory, and instrumental parameters during the study. In addition, the symptom of diarrhea (stool with a frequency of more than 3 times a day of type 6 and 7 according to the Bristol stool scale), including its frequency, duration, and the number of bowel movements of loose stool per day were precisely evaluated in both groups. RESULTS: In the overall patient pool, diarrhea was reported in 21.7% of in-patients during the observation period (95% confidence interval [CI] 14.2-29.1) with a mean duration of 4.6154 days (95% CI 3.7910-5.4398). The incidence of diarrhea in group 1 was 13.3% (95% CI 4.5-22.2), and in group 2, it was 30.0% (95% CI 18.1-41.9). Relative risk showed that the use of the S. boulardii CNCM I-745 probiotic drug leads to a significant reduction in the risk of diarrhea in hospitalized patients with COVID-19 infection receiving antibiotic therapy (odds ratio [OR] 0.3590, 95% CI 0.1421-0.9069; p=0.0303). In group 1, the duration of diarrhea was 3.1250 days (95% CI 2.5892-3.6608) versus 5.2778 days (95% CI 4.2290-6.3265) in group 2, p=0.0112. The mean daily frequency of loose stools in patients with diarrhea in group 1 was 3.2500 (95% CI 2.6588-3.8412) versus 4.3889 (95% CI 3.7252-5.0525) in group 2, p=0.0272. The secondary endpoint, duration of hospital stay, was also significantly shorter in group 1 patients - 11.6833 days (95% CI 11.2042-12.1625) versus 12.7333 days (95% CI 12.1357-13.3309) in group 2, p=0.0120. CONCLUSION: The present prospective comparative study demonstrated that adding S. boulardii CNCM I-745 probiotic drug into the standard treatment regimen of patients with new coronavirus infection COVID-19 receiving antibiotic therapy helps reduce the incidence of diarrhea and its severity during hospitalization, as well as the duration of hospital stay.

Translating Microbiome Research From and To the Clinic.

Extensive research has elucidated the influence of the gut microbiota on human health and disease susceptibility and resistance. We review recent clinical and laboratory-based experimental studies associating the gut microbiota with certain human diseases. We also highlight ongoing translational advances that manipulate the gut microbiota to treat human diseases and discuss opportunities and challenges in translating microbiome research from and to the bedside.

Health Benefits of Consuming Foods with Bacterial Probiotics, Postbiotics, and Their Metabolites: A Review.

Over the years, probiotics have been extensively studied within the medical, pharmaceutical, and food fields, as it has been revealed that these microorganisms can provide health benefits from their consumption. Bacterial probiotics comprise species derived from lactic acid bacteria (LAB) (genus Lactobacillus, Leuconostoc, and Streptococcus), the genus Bifidobacterium, and strains of Bacillus and Escherichia coli, among others. The consumption of probiotic products is increasing due to the current situation derived from the pandemic caused by COVID-19. Foods with bacterial probiotics and postbiotics are premised on being healthier than those not incorporated with them. This review aims to present a bibliographic compilation related to the incorporation of bacterial probiotics in food and to demonstrate through in vitro and in vivo studies or clinical trials the health benefits obtained with their metabolites and the consumption of foods with bacterial probiotics/postbiotics. The health benefits that have been reported include effects on the digestive tract, metabolism, antioxidant, anti-inflammatory, anticancer, and psychobiotic properties, among others. Therefore, developing food products with bacterial probiotics and postbiotics is a great opportunity for research in food science, medicine, and nutrition, as well as in the food industry.

Mapping the output of the global literature on the links between gut microbiota and COVID-19.

BACKGROUND: The term "human microbiota" refers to populations of microorganisms that live harmoniously in co-existence with humans. They contribute significantly to the host's immunological response when confronted with a respiratory viral infection. However, little is known about the relationship between the human microbiome and COVID-19. Therefore, our objective is to perform a bibliometric analysis to explore the overall structure and hotspots of research activity on the links between microbiota and COVID-19 at the global level. METHODS: The research literature on the microbiota and COVID-19 published between 2020 and 2022 was obtained from the Scopus database. Bibliometric analysis and network visualization were performed with VOSviewer. RESULTS: Of the 701 publications selected, the USA contributed the most (n = 157, 22.40%), followed by China (n = 118, 16.83%) and Italy (n = 82, 11.70%). Hotspots in this field were "COVID-19 is associated with an altered upper respiratory tract microbiome," "the effect of antibiotics on the gut microbiome," as well as "patient nutrition and probiotic therapy in COVID-19." CONCLUSIONS: The links between microbiota and COVID-19 remain an urgent concern at present, and the use of probiotics or/and antibiotics during the pandemic needs to be further improved. This landscape analysis of the links between the microbiota and COVID-19 will provide a basis for future research.

Effect of a Multi-Strain Probiotic Supplementation to Manage Stress during the COVID-19 Pandemic: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial.

INTRODUCTION: The COVID-19 pandemic strongly affected every aspect of the modern society, from health to socioeconomics, leading people to experience high levels of stress. METHODS: A double-blind, cross-over, placebo-controlled clinical study was performed to investigate the ability of a food supplement containing two probiotic strains, Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077, in supporting 33 healthy adults, working at a university, in stress management. The efficacy of the tested strains in influencing the stress response, in terms of mood and sleep behavior, was assessed using the following validated questionnaires: Profile of Mood State (POMS) and Pittsburgh Sleep Quality Index (PSQI). RESULTS: Outcomes of the POMS and the PSQI demonstrated a significant reduction of the questionnaire's scores both versus baseline and placebo after 30 days of probiotic intake. CONCLUSIONS: According to the results, the probiotic food supplement investigated showed a remarkable effect on stress management by improving the quality of sleep and the mood.

Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19.

Spore-based Bacillus probiotic treatment improves intestinal health. The intestinal microbiota influences both the innate and adaptive immune responses. As such, the influence of ongoing spore-based probiotic treatment (five probiotic strains of Bacillus) on the clinical outcomes of mild COVID-19 was evaluated in this retrospective, observational study. Demographics, medical history, probiotic use, and COVID-19 symptom information were collected. The study included 120 patients with a PCR-confirmed SARS-CoV-2 infection and mild COVID-19 symptoms. The probiotic group (n = 60) comprised patients with ongoing probiotic treatment (≥1 month); the control group comprised patients not taking probiotics (n = 60). The primary outcome was time to symptom resolution; secondary outcomes included time to fever resolution and presence of digestive symptoms. The probiotic group had a significantly shorter time to symptom resolution (mean (95% confidence interval) days: control group, 8.48 (6.56, 10.05); probiotic group, 6.63 (5.56; 6.63); p = 0.003) and resolution of fever (control group, 2.67 (1.58, 3.61); probiotic group, 1.48 (1.21, 2.03); p < 0.001). More patients in the probiotic group (n = 53) than in the control group (n = 34) did not have digestive symptoms (p < 0.001). Among adults with mild COVID-19, participants receiving ongoing probiotic treatment had a shorter clinical course, and fewer had digestive symptoms compared with those not taking probiotics.

Evaluating a physicians' perspective on the use of probiotics and vitamins against coronavirus disease.

OBJECTIVE: To evaluate the perspective of family physicians on probiotics and vitamins against coronavirus disease-2019. METHODS: The cross-sectional study was conducted from June 1 to 30, 2021, after approval from the ethics review committee of Bursa Uludag University, Bursa, Turkey, and comprised family physicians of either gender working at family health centres in the country. Data was collected using an online questionnaire to measure the sociodemographic characteristics, habits, health status related to coronavirus disease-2019, and their knowledge, awareness and behaviour towards the use of probiotics and vitamins during the pandemic. Data was analysed using SPSS 25. RESULTS: Of the 218 family physicians, 130(59.6%) were male and 88(40.4%) were female. The overall mean age was 46.82±5.85 years, mean professional experience was 22.32±8.75 years, and mean experience in family medicine was 10.14±3.51 years. The knowledge and awareness level about coronavirus disease-2019 was high 4.18±0.58, exposure to the disease 3.36±0.83 and their inclination towards the use of vitamins and probiotics 1.68±0.75 was low. Among the participants, 90(41.3%) used probiotic products and 120(55%) used drugs, such as vitamins and minerals. Vitamin C 99(45.4%) was the most commonly used supplement. CONCLUSIONS: Physicians' knowledge and awareness and a realistic scientific approach are important when recommending supplements, such as probiotics, vitamins and minerals, to individuals during the pandemic.

The Contribution of Diet Therapy and Probiotics in the Treatment of Sarcopenia Induced by Prolonged Immobilization Caused by the COVID-19 Pandemic.

The prolonged immobilization associated with COVID-19 infection and the restrictions imposed by the pandemic have determined major changes in physical activity and eating habits, with a negative impact on physical performance. This study monitored non-pharmacological interventions (diet therapy and probiotics) in managing sarcopenia for patients with recent SARS-CoV-2 history (14 days). A prospective study was performed on 200 patients (between December 2020-December 2021), with SPPB score < 9, randomly divided into: Group K-DP (93 patients) with dietary therapy (protein 1.2-1.5 g/kg) and probiotics for two months; and Group K-non-DP (107 patients) without diet therapy and probiotics. All patients were included in a specific physical training program (40 min), three sessions per week. Skeletal muscle index (SMI), serum albumin, and hemoglobin were determined. The SMI was initially low for both groups without significant statistical differences (6.5 ± 0.52 kg/m2 for Group K-non-DP vs. 6.7 ± 0.57 Kg/m2 for Group K-DP, p = 0.135). After two months, significant difference between initial and final SMI values was determined for Group K-DP (6.92 ± 0.50 kg/m2 vs. 6.77 ± 0.56 kg/m2, p = 0.048). In Group K-DP, at end of study, were more patients with normal SMI (n = 32 → N = 70) values (p < 0.001) and fewer sarcopenia patients (p < 0.001). The initial serum albumin means values in the two groups (Group K-non-DP, 4.17 ± 1.04 g/dL, and Group K-DP, 3.95 ± 0.98 g/dL) were not statistically significantly different (p = 0.122). The hemoglobin level improved significantly following a hyper protein diet enriched with pro-biotics (p = 0.003). Diet therapy, consisting of increased protein intake and specific probiotics and specific physical therapy, demonstrated superiority in improving the functional status of patients with recent COVID-19 infection.

Antibiotics and probiotics impact gut antimicrobial resistance gene reservoir in COVID-19 patients.

Dysbiosis of gut microbiota is well-described in patients with coronavirus 2019 (COVID-19), but the dynamics of antimicrobial resistance genes (ARGs) reservoir, known as resistome, is less known. Here, we performed longitudinal fecal metagenomic profiling of 142 patients with COVID-19, characterized the dynamics of resistome from diagnosis to 6 months after viral clearance, and reported the impact of antibiotics or probiotics on the ARGs reservoir. Antibiotic-naive patients with COVID-19 showed increased abundance and types, and higher prevalence of ARGs compared with non-COVID-19 controls at baseline. Expansion in resistome was mainly driven by tetracycline, vancomycin, and multidrug-resistant genes and persisted for at least 6 months after clearance of SARS-CoV-2. Patients with expanded resistome exhibited increased prevalence of Klebsiella sp. and post-acute COVID-19 syndrome. Antibiotic treatment resulted in further increased abundance of ARGs whilst oral probiotics (synbiotic formula, SIM01) significantly reduced the ARGs reservoir in the gut microbiota of COVID-19 patients during the acute infection and recovery phase. Collectively, these findings shed new insights on the dynamic of ARGs reservoir in COVID-19 patients and the potential role of microbiota-directed therapies in reducing the burden of accumulated ARGs.

Gut bacteria, bacteriophages, and probiotics: Tripartite mutualism to quench the SARS-CoV2 storm.

Patients with SARS-CoV-2 infection, exhibit various clinical manifestations and severity including respiratory and enteric involvements. One of the main reasons for death among covid-19 patients is excessive immune responses directed toward cytokine storm with a low chance of recovery. Since the balanced gut microbiota could prepare health benefits by protecting against pathogens and regulating immune homeostasis, dysbiosis or disruption of gut microbiota could promote severe complications including autoimmune disorders; we surveyed the association between the imbalanced gut bacteria and the development of cytokine storm among COVID-19 patients, also the impact of probiotics and bacteriophages on the gut bacteria community to alleviate cytokine storm in COVID-19 patients. In present review, we will scrutinize the mechanism of immunological signaling pathways which may trigger a cytokine storm in SARS-CoV2 infections. Moreover, we are explaining in detail the possible immunological signaling pathway-directing by the gut bacterial community. Consequently, the specific manipulation of gut bacteria by using probiotics and bacteriophages for alleviation of the cytokine storm will be investigated. The tripartite mutualistic cooperation of gut bacteria, probiotics, and phages as a candidate prophylactic or therapeutic approach in SARS-CoV-2 cytokine storm episodes will be discussed at last.