Publications by authors named "Herbert DuPont"

Article Synopsis
  • Microbiota restoration therapy is a new treatment for a recurring infection called rCDI, using special products made from healthy gut bacteria.
  • Two main products have been approved: RBX2660 (REBYOTA™) and SER-109 (VOWST™), both aimed at preventing rCDI and helping doctors understand their differences.
  • Research shows these treatments are safe and effective, and they help restore a healthy balance of gut bacteria, which is important for fighting infections.
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Background: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.

Methods: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).

Results: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant.

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Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile.

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Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy.

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Background: Parkinson's disease is a heterogeneous neurodegenerative disorder with distinctive gut microbiome patterns suggesting that interventions targeting the gut microbiota may prevent, slow, or reverse disease progression and severity.

Objective: Because secretory IgA (SIgA) plays a key role in shaping the gut microbiota, characterization of the IgA-Biome of individuals classified into either the akinetic rigid (AR) or tremor dominant (TD) Parkinson's disease clinical subtypes was used to further define taxa unique to these distinct clinical phenotypes.

Methods: Flow cytometry was used to separate IgA-coated and -uncoated bacteria from stool samples obtained from AR and TD patients followed by amplification and sequencing of the V4 region of the 16 S rDNA gene on the MiSeq platform (Illumina).

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Background: Acute gastroenteritis (AGE) is a major medical condition for travellers worldwide, particularly travellers to low- and middle-income countries. Norovirus (NoV) is the most common cause of viral AGE in older children and adults, but data on prevalence and impact amongst travellers is limited.

Methods: Prospective, multi-site, observational cohort study conducted 2015-2017, amongst adult international travellers from the US and Europe to areas of moderate to high risk of travel-acquired AGE.

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Background: travellers' diarrhoea (TD) is frequently reported with incidence up to 40% in high-risk destinations. Previous studies showed that the number of loose stools alone is inadequate to holistically predict the severity of TD. To improve the prediction of prognosis and to optimize treatments, a simple risk-based clinical severity classification has been developed.

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Background And Purpose: The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease.

Methods: This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks.

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IgA-coated bacteria in the gut (IgA-biome) provide a homeostatic function in healthy people through inhibition of microbial invaders and by protecting the epithelial monolayer of the gut. The laboratory methods used to detect this group of bacteria require flow cytometry and DNA sequencing (IgA-Seq). With dysbiosis (reduced diversity of the microbiome), the IgA-biome also is impaired.

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Abu-'Ali al-Husayn ibn Abdallah ibn-Sina (known in the West as Avicenna) is revered in much of Asia as one of history's greatest physicians. And yet, few westerners know of him, his iconic Canon of Medicine or the role he played in preserving ancient Greek medical knowledge following the sack of Rome. We briefly review Avicenna's impressive legacy and provide what to our knowledge is the first critical examination of the illness responsible for his death at age 58 years.

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Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing UTIs in a patient with an ileal conduit and urostomy.

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Article Synopsis
  • The study focuses on RBX2660, a new investigational treatment for recurrent Clostridioides difficile infection (rCDI), showing promising safety and efficacy compared to standard antibiotics.
  • In a Phase 2 trial, RBX2660 achieved a 78.9% treatment success rate, significantly higher than the 30.7% success rate of a historical control group.
  • Notably, 91% of patients treated with RBX2660 remained free from CDI for 24 months, suggesting long-lasting effectiveness.
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Background: Clostridioides difficile infection (CDI) is a leading cause of hospital-associated antibiotic-related diarrhea and deaths worldwide. Vancomycin is one of the few antibiotics recommended for both nonsevere and severe CDI cases. We sought to determine whether vancomycin nonsusceptible C.

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Article Synopsis
  • Secretory IgA (SIgA) plays a crucial role in both defending the host and shaping microbial communities on mucosal surfaces by regulating which microbes are included or excluded and influencing bacterial gene expression.
  • A recent study analyzed the IgA-Biomes in Mexican-American adults and found differences in SIgA-coated bacteria across varying glycemic levels, especially in relation to inflammation associated with type 2 diabetes.
  • This research highlights a relationship between the balance of pro-inflammatory and anti-inflammatory T-cells (Th17:Treg ratios) and microbial diversity in the gut, offering new insights into how immune responses affect microbiomes and chronic inflammatory diseases.
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Cancer patients are at increased risk of recurrent Clostridioides difficile infection (rCDI) due to malignancy itself, cancer therapy, and frequent antibiotic use and have a lower response rate to standard oral antibiotics. There are limited data on the safety and efficacy of fecal microbiota transplantation (FMT) for treating rCDI in cancer patients. We aim to describe our experience of using FMT to treat rCDI at a tertiary cancer center.

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Opportunistic pathogenic bacteria may cause disease after the normally protective microbiome is disrupted (typically by antibiotic exposure). Clostridioides difficile is one such pathogen having a severe impact on healthcare facilities and increasing costs of medical care. The search for new therapeutic strategies that are not reliant on additional antibiotic exposures are currently being explored.

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Background: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.

Methods: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors.

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Purpose Of Review: To provide the definition, causes, and current recommendations for workup and treatment of acute infectious colitis in adults, a common medical problem of diverse cause.

Recent Findings: The management of acute colitis in adults depend upon establishment of cause. Most forms of infectious colitis are treatable with antimicrobials.

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Mucosal surfaces like those present in the lung, gut, and mouth interface with distinct external environments. These mucosal gateways are not only portals of entry for potential pathogens but also homes to microbial communities that impact host health. Secretory immunoglobulin A (SIgA) is the single most abundant acquired immune component secreted onto mucosal surfaces and, via the process of immune exclusion, shapes the architecture of these microbiomes.

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Background: Renal impairment is not a consistently cited risk factor for recurrent infection (rCDI). We examined the association between renal impairment and rCDI and the effect of bezlotoxumab, an anti-toxin B monoclonal antibody, in reducing rCDI in participants with renal impairment.

Methods: We pooled data from 2 randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trials conducted in participants receiving bezlotoxumab or placebo infusion during oral antibacterial drug treatment for CDI.

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The Human Microbiome Initiative of NIH, begun in 2007, has opened the door to the power of the intestinal microbiome in health and disease. The 100 trillion gut microbes influence body function through three pathways: (1) via the neural route where 500 million neurons of the enteric nervous system (the body's second brain) connect to the brain and spinal cord, (2) via the immune route where the gut-immune capacity prevents infection and elicits immune response to vaccines, and (3) by the hormonal route wherein biologically active chemicals are released from enteroendocrine cells to control mood and body functions. Through research, the identification of diseases and disorders associated with abnormal microbiome ("dysbiosis") has increased in number with potential for reversibility.

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Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with a multifactorial pathophysiology. The gut microbiota differs between patients with IBS and healthy individuals. After a bout of acute gastroenteritis, postinfection IBS may result in up to approximately 10% of those affected.

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Reduction in diversity of the intestinal microbiome (dysbiosis) is being identified in many disease states, and studies are showing important biologic contributions of microbiome to health and disease. Fecal microbiota transplantation (FMT) is being evaluated as a way to reverse dysbiosis in diseases and disorders in an attempt to improve health. The published literature was reviewed to determine the value of FMT in the treatment of medical disorders for which clinical trials have recently been conducted.

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