Publications

BMJ Open Gastroenterology

The objective of this study was 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. 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 [...]

Frontiers in Microbiology 

Ivermectin is an anti-parasitic agent that has gained attention as a potential COVID-19 therapeutic. It is a compound of the type Avermectin, which is a fermented by-product of Streptomyces avermitilis. Bifidobacterium is a member of the same phylum as Streptomyces spp., suggesting it may have a symbiotic relation with Streptomyces. Decreased Bifidobacterium levels are observed in COVID-19 susceptibility states, including old age, autoimmune disorder, and obesity. We hypothesize that Ivermectin  [...]

Future Medicine

Aims: Ivermectin is a safe, inexpensive and effective early COVID-19 treatment validated in 20+ random, controlled trials. Having developed combination therapies for Helicobacter pylori, the authors present a highly effective COVID-19 therapeutic combination, stemming from clinical observations. Patients & methods: In 24 COVID-19 subjects refusing hospitalization with high-risk features, hypoxia and untreated moderate to severe symptoms averaging 9 days, the authors administered this novel combination of ivermectin, doxycycline, zinc and vitamins D and C. Results & conclusions: All subjects  

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Future Medicine

Vitamin C, also known as ascorbic acid, is used as a supplement for fighting infectious disorders. Many disorders, including COVID-19 and cancer, harmfully disrupt the levels of bacteria that naturally reside in the gut, which may contribute to symptoms. The aim of the study was to understand whether high-dose vitamin C could improve the types of bacteria in the human gut. To do this we characterized the gut bacteria before and after 23 individuals took vitamin C, as prescribed by their respective physicians. We observed [...]

International Journal of Medical Science and Clinical Invention 

The Human Microbiome Project, launched in in 2007, and the discovery of innate lymphoid cells (ILCs) in 2008 are major advances that have begun to shed light on the pathogenesis of some disorders of uncertain etiology, including autoimmune, fibrotic, and neuropsychiatric illnesses, as well as the potential interaction of systemic infections with the gut-brain axis. 

The gut microbial community is immunologically ―tolerated‖ in the gastrointestinal (GI) tract but may elicit immunogenicity and pathology upon translocation into host tissues (1) (2). Indeed, in the former case long- term, low-grade inflammation may eventually lead to disease (3), while in the latter case, numerous studies have reported the presence of intestinal microbes and/or their molecules as part of observed pathology within host tissues, such as the circulatory system and the brain (4) (5).  [...]

Endocrines

Similar to previous pandemics, COVID-19 has been succeeded by well-documented post-infectious sequelae, including chronic fatigue, cough, shortness of breath, myalgia, and concentration difficulties, which may last 5 to 12 weeks or longer after the acute phase of illness. Both the psychological stress of SARS-CoV-2 infection and being diagnosed with COVID-19 can upregulate cortisol, a stress hormone that disrupts the efferocytosis effectors, macrophages, and natural killer cells, leading to the excessive accumulation of senescent cells and disruption of  [...]

Advances In Clinical And Medical Research

We read with great interest the article by Ambati BK, et al. “MSH3 Homology and Potential Recombination Link to SARS-CoV-2 Furin Cleavage Site” published on February 21st, 2022 in Frontiers in Virology. This perspective paper highlights a 19-nucleotide genetic sequence, a reverse complement of the human MSH3 gene, that contains the SARS-CoV-2 furin cleavage site (FCS). As this sequence (SEQ ID11652) was patented by Moderna in 2016 (US patent 9,587,003), some have suggested that the FCS may have been known prior to the COVID-19 pandemic [1]. 

Aside from its well-established role in averting tumor genesis, novel preclinical studies found that MSH3 is a key regulator of short tandem repeats  [...]

A recent study by Ahrens AP, et al. on university students with suicidal ideation has highlighted the connection between immunity and psychopathology, especially major depressive disorder (MDD) and suicidality (1)(2)(3). This study has found that four major histocompatibility complex (MHC) alleles and the absence of oral microbe Alloprevotella rava increase the risk of suicidal behavior, emphasizing a microbial-genetic link in this pathology.   [...]

Frontiers in Immunology    

We read with great interest the paper by Beaudoin CA et al. “Are There Hidden Genes in DNA/RNA Vaccines?”, reporting overlapping sequences between the SARS-CoV-2 spike (S) glycoprotein and two viral genes (1). If translated, the undesired proteins may cause rare, 

untoward effects, including those recorded in Vaccine Adverse Event Reporting System (VAERS). 

These findings are in line with our own research and that of others however, aside from overlapping genes (OLGs), the S protein also contains overlapping molecular structures and signals (heptad repeats, simple sequence repeats, calcium calmodulin kinase II, and prion-like domains) that can lead to VAERS-recorded pathology (2-6).   [...]

Frontiers in Microbiology 

The messenger RNA (mRNA) vaccines for COVID-19, Pfizer-BioNTech and Moderna, were authorized in the US on an emergency basis in December of 2020. The rapid distribution of these therapeutics around the country and the world led to millions of people being vaccinated in a short time span, an action that decreased hospitalization and death but also heightened the concerns about adverse effects and drug-vaccine interactions. The COVID-19  [...]

Case Reports in Gastroenterology 

Our index patient is a 19-year-old man with Crohn’s disease. After developing symptoms con- sistent with COVID-19, he, his 62-year-old father, and 14-year-old sister tested positive for SARS-CoV-2 in May 2020. Despite a shared household, his 50-year-old mother with a history of asthma and his healthy brother and sister-in-law (a married couple) remained negative. The index patient and his mother had undergone microbiome analysis in May 2019, following his brother and his sister-in-law in November 2020. We observed significant differences between the fecal microbiota of the SARS-CoV-2-positive [...]

ACG CASE REPORTS JOURNAL 

We present a case of an ectopic stomach visualized intraoperatively at the site of intestinal intussusception via surgeon-assisted advancement of the endoscope. Heterotopic gastric mucosa, also known as an ectopic stomach, refers to the discovery of gastric tissues in an organ or tissue distinct from, and without vascular or anatomical continuity with, the main body of the normal stomach. In our case, an 18-year-old woman presented to the emergency department with jejunal intussusception. During emergency laparotomy, a large pedunculated mass was visualized and later confirmed histopathologically to be an ectopic stomach.

Journal of Next Generation Sequencing & Applications 

Toxigenic Clostridioides Difficile Infection (CDI) is the most common cause of nosocomial disease in the United States. However, the prevalence in the general population of toxigenic and non-toxigenic strains is poorly understood. In this cross-sectional study we sought to determine the presence of Clostridioides difficile colonizing a representative sample of 119 CDI-asymptomatic volunteers (health care providers, public with chronic conditions, and healthy public).

Reports have been surfacing surrounding CNS-associated symptoms in individuals affected by coronavirus disease 19 (COVID-19). Tourette syndrome is a neuropsychiatric disorder with usual onset in childhood. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. The authors of this case report describe Tourette’s-like symptoms in a patient resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupting gut microbiota.

Journal of Clinical Trials

Malignant Pleural Mesothelioma (MPM) is a highly aggressive and almost universally fatal neoplasm with limited treatment options. The role of the programmed cell death protein 1 (PD-1) pathway has garnered attention due to its role in eliciting the immune checkpoint response of T cells, resulting in evasion of tumor cells from immune surveillance and chemotherapy resistance. [...]

Gastroenterology Research

The effectiveness of fecal microbiota transplantation (FMT), a treatment for Clostridioides difficile infection (CDI), is dependent on successful engraftment (incorporation) of donor stool. We present a method for evaluating engraftment success based on next-generation sequencing (NGS)-based profiling of bacterial strains present in donor and recipient stool, and we suggest its potential to guide treatment decisions.

MedRXiv (Preprint)

Ivermectin is a safe, inexpensive and effective early COVID-19 treatment validated in 20+ RCTs. Having developed combination therapies for Helicobacter pylori, we tested various COVID-19 combinations and describe the most effective. In 24 consecutive COVID-19 subjects with high risk features, hypoxia and untreated moderate-severe symptoms averaging 9 days, we trialed this novel combination comprising ivermectin, doxycycline, zinc, and Vitamins D and C. It was highly effective. [...]

Journal of Clinical Trials

Several reports have raised safety concerns regarding the use of probiotics. To address these concerns, this study examined the relative abundance (proportion of the microbiome made up of a particular taxa) and normalized read counts (number of times a particular microbe was identified) of Bifidobacteria in the gut microbiome of healthy subjects participating in an ongoing study on the microbiome. Bifidobacteria is a critically important constituent of the human microbiome and plays roles in digestion, gut immunity, and cancer [...]

   International Journal of Molecular Sciences / Vol. 22 / Issue 13

Concerns are emerging that a high-fat diet rich in n-6 PUFA (n-6HFD) may alter gut microbiome and increase the risk of intestinal disorders. Research is needed to model the relationships between consumption of an n-6HFD starting at weaning and development of gut dysbiosis and colonic inflammation in adulthood. We used a C57BL/6J mouse model to compare the effects of exposure to a typical American Western diet (WD) providing 58.4%, 27.8%, and 13.7% energy (%E) from carbohydrates, fat, and protein, respectively, with those of an isocaloric and isoproteic soybean oil-rich n-6HFD providing 50%E and 35.9%E from total fat and carbohydrates, respectively on gut inflammation and microbiome profile. Methods: At weaning, male offspring were assigned to either the WD or n-6HFD through 10–16 weeks of age. The WD included fat exclusively from palm oil whereas the n-6HFD contained fat exclusively from soybean oil. We recorded changes in body weight, cyclooxygenase-2 (COX-2) expression, colon histopathology, and gut microbiome profile. Results: Compared to the WD, the n-6HFD increased plasma levels of n-6 fatty acids; colonic expression of COX-2; and the number of colonic inflammatory and hyperplastic lesions. At 16 weeks of age, the n-6HFD caused a marked reduction in the gut presence of Firmicutes, Clostridia, andLachnospiraceae, and induced growth of Bacteroidetes and Deferribacteraceae. At the species level, then-6HFD sustains the gut growth of proinflammatory Mucispirillum schaedleri and Lactobacillus murinus.Conclusions: An n-6HFD consumed from weaning to adulthood induces a shift in gut bacterial profile associated with colonic inflammation.

Journal of Experimental Pathology / Vol. 2 / Issue 2

In this mini-review, we summarise the significant body of evidence for the treatment of Clostridioides difficile infection (CDI) with Faecal Microbiota Transplantation (FMT) and propose the transition of FMT from ‘last resort’ treatment to the forefront of CDI management. To address the feasibility of this proposal, we examined the rates of efficacy in FMT treated patients with CDI and also reviewed the safety of FMT across available published studies. A considered view of safety, efficacy, product standardisation, quality control and Good Manufacturing Practices (GMP) allows for a prudent approach in positioning FMT as the primary or initial treatment for CDI.

The American Journal of Gastroenterology / Vol. 115 / Issue - p S1196 

Crohn's disease (CD) is a chronic relapsing inflammatory disease that can affect any part of the GI tract. Recent evidence suggests that changes in the composition of gut microbiota are a common feature in CD. This is paving the way for novel therapeutics that target the microbiome. Recently, serum-derived bovine Ig/protein isolate (SBI) has emerged as a novel therapeutic for different GI pathologies. SBI is uniquely designed to increase gut Ig levels, over 50% of which is IgG. SBI works by neutralizing microbial components, maintaining gut microbiota, managing gut barrier function, and sustaining GI immune balance. We present a patient with CD who sought to avoid immune-suppression. We introduced SBI to modify the composition of the gut microbiome, restore intestinal diversity and thus achieve clinical remission.

 Reviews in Cardiovascular Medicine  / Vol. 21  / Issue (4)

The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes...

 Children /  Vol. 7  / Issue 12 

The gut microbiome profile of a child with autism spectrum disorder (ASD) and co-occurring gastrointestinal (GI) symptoms was compared to that of her healthy triplet siblings to determine if she exhibited intestinal dysbiosis. Shotgun metagenomic sequencing was performed in individual fecal samples, and relative microbial abundance and diversity was determined. Microbial diversity was lower in sibling #3, coupled with a higher Bacteroidetes/Firmicutes ratio, a lower relative abundance of Actinobacteria, and an increased relative abundance of Proteobacteria. Our findings are suggestive of gut dysbiosis in a child with ASD and co-occurring GI symptoms, compared to her two healthy triplet siblings.

The New England Journal of Medicine

Eosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate treatments. Mast-cell activity may contribute to the pathogenesis of the conditions. AK002 (lirentelimab) is an anti–Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis.

Journal of International Medical Research

Alzheimer’s disease (AD), the most common form of dementia, is a leading cause of death and a major cause of morbidity in older people. The disease is characterized by progressive memory loss, cognitive impairment, and the cerebral accumulation of amyloid-b peptide. Given the health and economic impacts of AD, treatments that target the underlying etiology of AD or modify the course of the disease are of significant interest. The gut microbiome has been increasingly implicated  [...]

Gastroenterology / Vol. 158 / Issue 6

Toxigenic Clostridioides difficile infection (CDI) is the most common cause of nosocomial disease in the United States, however, its prevalence in the general population is poorly understood. In this study we sought to determine the presence of Clostridioides difficile colonizing a representative sample of 119 asymptomatic adult volunteers, 12 of which were physicians treating patients with CDI. Methods: Next generation sequencing (NGS) was performed on fecal samples from [...]

The American Journal of Gastroenterology / Vol. 114

Pathogenic Clostridioides difficile (C. difficile) is the most common cause of nosocomial infection in the United States. However, the prevalence of C. difficile colonization in the general population is poorly understood. We sought to determine the presence and nature of various C. difficile strains colonizing a representative sample of 17 asymptomatic adult volunteers, consisting of 10 healthy and 7 stable Crohn's patients.

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Sabine Hazan, MD,  Series Editor

In this article, we discuss further understanding the gut microbiome along with its effect on metabolites and cardiovascular health. This understanding will give us opportunities to develop new test and therapeutic approaches to arteriosclerosis. In the future, stool transplantation with lean or low risk for cardiovascular disease microflora may be a way of treating patients who are susceptible to [...]

Sabine Hazan, MD,  Series Editor

There is a growing body of research suggesting that obesity, metabolic syndrome, and insulin resistance are associated with predictable phyla and gene level compositional changes in the intestinal microbiome of humans and mice. With a better understanding of these changes, we can develop new, robust therapeutic strategies. In this article, we will briefly discuss some of the definitive research related to  [...]

Sabine Hazan, MD,  Series Editor

A new, emerging paradigm suggests that the susceptibility, severity, and duration of some diseases, even some previously thought to be independent of microbial involvement, are mediated by a complex interplay of host and microbe genomes. Already, nearly 10 million different microbial genes have been isolated from the human gut. In this series, we aim to shed light on some of the most promising research to date that [...]

Sabine Hazan, MD,  Series Editor

An IBD patient’s quality of life can be significantly diminished when treated with conventional therapies. However, like the trend of fecal microbiota transplantation (FMT) for the treatment of Clostridium difficile infection, there is promising evidence that a similar approach will prove efficacious in treating UC and Crohn’s, especially given the increasingly predictable intestinal microbiome perturbation 

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Sabine Hazan, MD,  Series Editor

Simply and elegantly defined by Lynch and Pedersen in their December 2016 article in the New England Journal of Medicine, a microbiome is the collection of all genomes of microbes in an ecosystem. In the context of human beings and our health, it is the vastly diverse genetic information observable in the microbes colonizing the distal GI tract.  Historically, the study of human microbiology has been one of a [...]

Background Clostridium difficile infection is the most common health-care-associated infection in the USA. We assessed the safety and efficacy of ridinilazole versus vancomycin for treatment of C difficile infection. Methods We did a phase 2, randomised, double-blind, active-controlled, non-inferiority study. Participants with signs and symptoms of C difficile infection and a positive diagnostic test result were recruited from 33 centres in the USA and Canada and randomly assigned (1:1) [...]