Development of indigestible IgA antibody for restoring microbiome balance

Dysbiosis, especially in the gut plays a crucial role in the pathogenesis of a wide variety of diseases, including inflammatory bowel disease, colorectal cancer, cardiovascular disease, obesity, diabetes and multiple sclerosis. At mucosal surfaces, mucosal polymeric immunoglobulin A（IgA）antibodies are known to be important to regulate the gut microbiota as well as to exclude infection induced by pathogenic bacteria or virus such as influenza and SARS-CoV-2（severe acute respiratory syndrome coronavirus 2）. Since the 1970s, oral administration of IgA or IgG antibodies has been performed against infectious enteritis caused by pathogenic Escherichia coli or Clostridioides difficile. However, none of them has been successfully developed as an antibody drug up to now. Although IgA is well known to modulate the gut commensal microbiota, the therapeutic IgA drugs to treat dysbiosis has not been developed. Here, we discuss the advantages of therapeutic IgA antibodies.Alternate :抄録Dysbiosisは、健康な微生物叢と比較した微生物組成の変化であり、腸内微生物多様性の減少および微生物分類群の変化を特徴とする。腸内のdysbiosisはまた、炎症性腸疾患、結腸直腸がん、心血管疾患、肥満、糖尿病および多発性硬化症を含むさまざまな疾患の病因において重要な役割を果たすと提唱されている。腸の多量体免疫グロブリンA（IgA）抗体は、腸内微生物叢を調節するだけではなく、病原性細菌、インフルエンザやSARS-CoV-2（重症急性呼吸器症候群コロナウイルス2）などのウイルス感染を粘膜部位から排除するのに重要であることが、多くのエビデンスから示されている。1970年代以降、治療用IgAまたはIgGの経口投与試験が、主に病原性大腸菌またはディフィシル菌によって引き起こされる感染性腸炎を治療するために行われてきた。しかし、現在まで臨床応用として開発に成功したものはない。腸内病原体に対する防御機能に加えて、IgAは腸内共生微生物叢を調節して共生に導くことがよく知られているが、dysbiosisを治療するためのIgA治療薬の開発も進んでいない。本稿では、治療用IgA抗体の利点とその開発について議論する。

A comprehensive nutritional support perspective in patients with COVID-19: a review

Purpose>Coronavirus disease-2019 (COVID-19) is becoming a crucial health problem worldwide. Continued and high-speed mutations of this virus result in the appearance of new manifestations, making the control of this disease difficult. It has been shown that well-nourished patients have strong immune systems who mostly have short-term hospitalization compared to others. The purpose of this study is to review the major nutrients involved in the immune system reinforcement and to explain nutritional aspects during the recovery of COVID-19.Design/methodology/approach>In this review paper, the mechanistic role of nutrients in boosting the immune system and the nutritional aspects during the recovery of COVID-19 patients were discussed. Papers indexed in scientific databases were searched using antioxidants, COVID-19, inflammation, immune system, macronutrient, micronutrient and probiotic as keywords from 2000 to 2022.Findings>Because of the adverse effects of drugs like thrombosis, pulmonary embolism and hypercholesterolemia, a balanced diet with enough concentrations of energy and macronutrients could increase the patient's durability. The inflammatory cytokines in a vicious cycle delay patients' rehabilitation. The main mechanistic roles of micronutrients are attributed to the downregulation of virus replication and are involved in energy homeostasis. Dysbiosis is defined as another disturbance among COVID-19 patients, and supplementation with beneficial strains of probiotics helps to exert anti-inflammatory effects in this regard. Being on a well-planned diet with anti-inflammatory properties could reverse cytokine storms as the major feature of COVID-19. Future studies are needed to determine the safe and effective dose of dietary factors to control the COVID-19 patients.Originality/value>Being on a well-planned diet with anti-inflammatory properties could reverse cytokine storms as the major feature of COVID-19. Future studies are needed to determine the safe and effective dose of dietary factors to control the COVID-19 patients.

Pathobiome Transformation and Features of Enteral Insufficiency in Patients with Peritonitis during the Covid-19 Pandemic

We studied the features of acute enteral failure in patients with peritonitis in the setting of COVID-19 by studying the properties of the enteral pathobiome, biochemical, functional, pro-inflammatory and anti-apoptotic markers in diffuse peritonitis. A retrospective randomized cohort controlled study was conducted;it included 84 patients divided into two groups. Stratified randomization was used. The species composition and properties of the enteral luminal pathobiome were studied. 699 inoculations were made, resulting in 3024 isolates. The enteral morphofunctional coefficient, the level of alkaline phosphatase and its intestinal isoform were dynamically studied. In immunohistochemical studies, we studied the expression of CD-3 and Bcl-2. Patients with COVID-19 in addition to a decrease in the level of saprophytic microflora, showed a significant increase in Klebsiella spp., Candida, Clostridium spp. and Citrobacter (p <= 0.05). The rate of antibiotic resistance in the comparison group was 8.3%, in the main group - 36.9%. MRSA pathogens were noted in 86.4% of cases, VRSA strains were found in 20.6% of cases. Patients with COVID-19 had a deficiency of intestinal alkaline phosphatase, which persisted even on the day 5 of treatment. Macro- and microscopic studies showed pronounced inflammatory and apoptotic changes in the intestinal wall of patients in the main group. A specific enteral pathobiome that is multiresistant to antibiotics, pronounced inflammatory and apoptotic changes in the intestinal wall, and a predisposition to perforation of the small intestine are characteristics of enteral failure in diffuse peritonitis in the setting of COVID-19.

Oral-Systemic Health and Disorders: Latest Advances on Oral–Gut–Lung Microbiome Axis

In particular, the bi-directional communication network, also known as the gut lung axis connecting the intestinal and pulmonary microbiota, is considered responsible for the massively increased bacterial load in the cecum after acute lung injury, causing alterations in airway microbiota and its transitory translocation into the bloodstream toward the bowel [7,8]. [...]subjects with chronic obstructive pulmonary disease often show intestinal hyper-permeability and a high prevalence of IBD [9]. Both mechanisms would underlie the association between periodontitis and inflammatory and degenerative diseases, such as atherosclerosis, Alzheimer’s disease, age-related macular degeneration [22], chronic inflammatory bowel disease [23], and solid neoplasms, such as colorectal carcinoma [24]. [...]intestinal microbes could, due to mucosal barrier impairment, translocate to the liver through the biliary tract and the portal vein, and oral dysbiosis could exacerbate chronic liver diseases, likely modulating the gut ecosystem through the oral–gut axis, on the one side, and may reflect the intestinal dysbiotic ecosystem, affected in turn by hepatic diseases, on the other side [12,25]. Furthermore, mainly the upper but also the lower airways of healthy individuals frequently harbor oral anaerobes, including Prevotella and Veillonella species, probably secondary to continuing microaspiration by contiguity. [...]detecting oral bacterial DNA in the lower airways in healthy subjects could represent the traces of aspirated oral bacteria either not eliminated through physiological clearance or living in dynamic equilibrium with host defensive responses by promoting mucosal immunity of the Th17/neutrophilic phenotype and suppressing innate immunity. Whether bacteria from the oral microbiome regulate responses to pulmonary pathogens and whether they interfere in inflammatory lung disease pathogenesis [26] is still under study. [...]a growing body of evidence highlights that gut and oral dysbioses, interconnected with the local microbial and inflammatory environment of the lung, liver, and other organs, are crucially implied in a multitude of diseases also involving distant organs.

The role of IL-36 subfamily in intestinal disease.

Interleukin (IL)-36 is a subfamily, of the IL-1 super-family and includes IL-36α, IL-36ß, IL-36γ, IL-38 and IL-36Ra. IL-36 cytokines are involved in the pathology of multiple tissues, including skin, lung, oral cavity, intestine, kidneys and joints. Recent studies suggest that IL-36 signaling regulates autoimmune disease in addition to antibacterial and antiviral responses. Most research has focused on IL-36 in skin diseases such as psoriasis, however, studies on intestinal diseases are also underway. This review outlines what is known about the bioactivity of the IL-36 subfamily and its role in the pathogenesis of intestinal diseases such as inflammatory bowel disease, colorectal cancer, gut dysbacteriosis and infection, and proposes that IL-36 may be a target for novel therapeutic strategies to prevent or treat intestinal diseases.

Apitherapy and Periodontal Disease: Insights into In Vitro, In Vivo, and Clinical Studies

Periodontal diseases are caused mainly by inflammation of the gums and bones surrounding the teeth or by dysbiosis of the oral microbiome, and the Global Burden of Disease study (2019) reported that periodontal disease affects 20–50% of the global population. In recent years, more preference has been given to natural therapies compared to synthetic drugs in the treatment of periodontal disease, and several oral care products, such as toothpaste, mouthwash, and dentifrices, have been developed comprising honeybee products, such as propolis, honey, royal jelly, and purified bee venom. In this study, we systematically reviewed the literature on the treatment of periodontitis using honeybee products. A literature search was performed using various databases, including PubMed, Web of Science, ScienceDirect, Scopus, clinicaltrials.gov, and Google Scholar. A total of 31 studies were reviewed using eligibility criteria published between January 2016 and December 2021. In vitro, in vivo, and clinical studies (randomized clinical trials) were included. Based on the results of these studies, honeybee products, such as propolis and purified bee venom, were concluded to be effective and safe for use in the treatment of periodontitis mainly due to their antimicrobial and anti-inflammatory activities. However, to obtain reliable results from randomized clinical trials assessing the effectiveness of honeybee products in periodontal treatment with long-term follow-up, a broader sample size and assessment of various clinical parameters are needed.

Obstructive Sleep Apnea as a Risk Factor for COVID-19 Severity—The Gut Microbiome as a Common Player Mediating Systemic Inflammation via Gut Barrier Dysfunction

The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the severity of COVID-19 outcomes (such as age, hypertension, diabetes mellitus, and obesity). Since many of these risk factors are known to be influenced by obstructive sleep apnea, this raises the possibility that OSA might be an independent risk factor for COVID-19 severity. A shift in the gut microbiota has been proposed to contribute to outcomes in both COVID-19 and OSA. To further evaluate the potential triangular interrelationships between these three elements, we conducted a thorough literature review attempting to elucidate these interactions. From this review, it is concluded that OSA may be a risk factor for worse COVID-19 clinical outcomes, and the shifts in gut microbiota associated with both COVID-19 and OSA may mediate processes leading to bacterial translocation via a defective gut barrier which can then foster systemic inflammation. Thus, targeting biomarkers of intestinal tight junction dysfunction in conjunction with restoring gut dysbiosis may provide novel avenues for both risk detection and adjuvant therapy.

OBEMIRISK‐Knowledge platform for assessing the risk of bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers

“Obemirisk – Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers” was a knowledge transfer project funded by the European Food Safety Authority (EFSA) that integrated a multidisciplinary team from Spain, France, Belgium, Slovakia and Poland. This project aimed to strengthen the knowledge capacity to assess the risk of bisphenol A and several structural analogues on gut microbiota that could mediate the obesogenic phenotype in childhood. Protocols and methodologies from different fields such as chemical analysis (food and biosamples), nutrition (surveys and questionnaires), microbiology (culturomics and metagenomics), and gene reporter assay (AhR‐Ligand) have been applied and shared. Several data generated under the project are available under open publications and databases for the Consortium and scientific community. Common documents and publications integrating data from endocrine disrupting chemicals (EDCs), bisphenols, microbiota dysbiosis and obesity were elaborated. A networking and specific capacity‐building programmes have been implemented to produce and share the new data on bisphenols data food composition, microbiota and its impact on obesity between providers and recipients’ partners. Scientific exchanges and specific designed courses provided training for students in the risk characterization related domains. The project was mainly focused on the bisphenols´ presence in consumed foods by Spanish children and in several children biosamples (saliva, urine, nails, and hair). Moreover, a pilot project on obese vs. normal‐weight children allowed to determine the obesity‐linked microbiota dysbiosis through metagenomics and specific biomarkers of the dysregulated microbiota‐immune system axis (AhR‐Ligands). The Obemirisk project applied a collaborative and multidisciplinary approach to establish scientific data compilation for harmonising risk assessment and to perform trainings on next generation of risk assessment where microbiome disruption might become a robust biomarker to be used in food safety. Several aspects of the process of capacity building have been mainly conceptual due to the COVId‐19 pandemic and will be further implemented through presential exchanges. Moreover, the consortium work strategy can also propose further EU collaborations for refining and elucidating the impact and mechanisms of bisphenols altering human microbiomes and triggering obesity. The knowledge, analyses and the integrative approach will be extrapolated for other foods, age ranges, geographical areas, and other biomatrices.For grant agreements: © OBEMIRISK consortium, 2022

IS IT POSSIBLE TO PREDICT VENTILATOR ASSOCIATED PNEUMONIA ETIOLOGY IN COVID-19 PATIENTS?

COVID-19 infection is no exception and may predispose to secondary bacterial and/or fungal co-infections like COVID-19 Associated Pulmonary Aspergillosis resulting in poor clinical outcomes especially among critically ill patients who require mechanical ventilation. Paolo Gaibani et al. conducted a prospective study (April to May, 2020) in a tertiary hospital in Bologna, Italy to assess the profile of the lower respiratory tract microbiome of critically ill patients with COVID-19 as compared to COVID-19 negative patients by using a 16S rRNA profiling on bronchoalveolar lavage samples. The dysbiosis observed in critically ill patients with COVID-19 was therefore characterized by the reduction of commensal bacterial species and predominance of opportunistic gram-negative pathogens frequently associated with multidrug resistance.