Using nutrition to help recovery from infections.

Purpose Of Review: Antibiotics are a cornerstone of modern medicine, but antibiotic consumption can have depleting effects on the gut microbiota, potentially leading to gastrointestinal symptoms and other diseases, namely Clostridioides difficile infection. Because nutrition is a major driver of gut microbiota diversity and function, here we explore the current evidence on the potential of diets in alleviate the deleterious effects of antibiotics consumed during infections.

Recent Findings: Beneficial nutrients can enhance the symbiotic effect of the gut microbiota with the host, supporting anti-inflammatory responses and maintaining tight junction integrity.

Clostridioides difficile infections; new treatments and future perspectives.

Purpose Of Review: As a significant cause of global morbidity and mortality, Clostridioides difficile infections (CDIs) are listed by the Centres for Disease Control and prevention as one of the top 5 urgent threats in the USA. CDI occurs from gut microbiome dysbiosis, typically through antibiotic-mediated disruption; however, antibiotics are the treatment of choice, which can result in recurrent infections. Here, we highlight new treatments available and provide a perspective on different classes of future treatments.

MiGut: A scalable in vitro platform for simulating the human gut microbiome-Development, validation and simulation of antibiotic-induced dysbiosis.

In vitro models of the human colon have been used extensively in understanding the human gut microbiome (GM) and evaluating how internal and external factors affect the residing bacterial populations. Such models have been shown to be highly predictive of in vivo outcomes and have a number of advantages over animal models. The complexity required by in vitro models to closely mimic the physiology of the colon poses practical limits on their scalability.

Profiling the Effects of Systemic Antibiotics for Acne, Including the Narrow-Spectrum Antibiotic Sarecycline, on the Human Gut Microbiota.

Treatment for moderate-to-severe acne vulgaris relies on prolonged use of oral tetracycline-class antibiotics; however, these broad-spectrum antibiotics are often associated with off-target effects and negative gastrointestinal sequelae. Sarecycline is a narrow-spectrum antibiotic treatment option. Here, we investigated the effect of prolonged sarecycline exposure, compared with broad-spectrum tetracyclines (doxycycline and minocycline) upon the colonic microbiota.

The potential of microbiome replacement therapies for Clostridium difficile infection.

Purpose Of Review: There is a paradox when treating Clostridium difficile infection (CDI); treatment antibiotics reduce C. difficile colonization but cause further microbiota disruption and can lead to recurrent disease. The success of faecal microbiota transplants (FMT) in treating CDI has become a new research area in microbiome restorative therapies but are they a viable long-term treatment option?

Recent Findings: C.

Can SARS-CoV-2 be transmitted via faeces?

Purpose Of Review: COVID-19 patients can present gastrointestinal symptoms, being diarrhoea one of the most frequent, suggesting intestinal health can be impacted by COVID-19. Here, we will discuss whether there is a correlation between the presence of SARS-CoV-2 RNA in faeces and diarrhoea, the relevance of gastrointestinal symptoms in disease diagnosis and transmission, and how COVID-19 can impact the gut microbial balance.

Recent Findings: SARS-CoV-2 RNA has been reported in faeces or rectal swabs of COVID-19 patients with and without diarrhoea, suggesting faecal shedding can occur independently of gastrointestinal symptoms.

The use of first-generation cephalosporin antibiotics, cefalexin and cefradine, is not associated with induction of simulated Clostridioides difficile infection.

Objectives: The use of broad-spectrum cephalosporins is associated with induction of Clostridioides difficile infection (CDI). Recent knowledge on the importance of the healthy microbiota in preventing pathogen colonization/outgrowth highlights the caution needed when prescribing broad-spectrum antibiotics. The use of historical narrow-spectrum antibiotics, such as first-generation cephalosporins, is gaining increased attention once more as they have a reduced impact on the microbiota whilst treating infections.

Trehalose-Induced Remodelling of the Human Microbiota Affects Infection Outcome in an Colonic Model: A Pilot Study.

Within the human intestinal tract, dietary, microbial- and host-derived compounds are used as signals by many pathogenic organisms, including . Trehalose has been reported to enhance virulence of certain ribotypes; however, such variants are widespread and not correlated with clinical outcomes for patients suffering from infection (CDI). Here, we make preliminary observations on how trehalose supplementation affects the microbiota in an model and show that trehalose-induced changes can reduce the outgrowth of , preventing simulated CDI.

Biofilms harbour Clostridioides difficile, serving as a reservoir for recurrent infection.

C. difficile infection (CDI) is a worldwide healthcare problem with ~30% of cases failing primary therapy, placing a burden on healthcare systems and increasing patient morbidity. We have little understanding of why these therapies fail.

Is there a causal relationship between trehalose consumption and Clostridioides difficile infection?

Purpose Of Review: Trehalose metabolism appears to play a role in the pathogenicity of some microbes. It has been claimed that trehalose consumption may be a risk factor for Clostridioides difficile infection (CDI), but the evidence for a causal link is contentious.

Recent Findings: Epidemic ribotypes of C.

A Novel, Orally Delivered Antibody Therapy and Its Potential to Prevent Infection in Pre-clinical Models.

infection (CDI) is a toxin-mediated infection in the gut and a major burden on healthcare facilities worldwide. We rationalized that it would be beneficial to design an antibody therapy that is delivered to, and is active at the site of toxin production, rather than neutralizing the circulating and luminal toxins after significant damage of the layers of the intestines has occurred. Here we describe a highly potent therapeutic, OraCAb, with high antibody titers and a formulation that protects the antibodies from digestion/inactivation in the gastrointestinal tract.

Eravacycline, a novel tetracycline derivative, does not induce Clostridioides difficile infection in an in vitro human gut model.

Objectives: The approval of new antibiotics is essential to combat infections caused by antimicrobial-resistant pathogens; however, such agents should be tested to determine their effect on the resident microbiota and propensity to select for opportunistic pathogens, such as Clostridioides difficile. Eravacycline is a new antibiotic for the treatment of complicated intra-abdominal infections. Here, we determined the effects of eravacycline compared with moxifloxacin on the microbiota and if these were conducive to induction of C.

Method comparison for the direct enumeration of bacterial species using a chemostat model of the human colon.

Background: Clostridioides difficile infection (CDI) has a high recurrent infection rate. Faecal microbiota transplantation (FMT) has been used successfully to treat recurrent CDI, but much remains unknown about the human gut microbiota response to replacement therapies. In this study, antibiotic-mediated dysbiosis of gut microbiota and bacterial growth dynamics were investigated by two quantitative methods: real-time quantitative PCR (qPCR) and direct culture enumeration, in triple-stage chemostat models of the human colon.

Clostridium difficile trehalose metabolism variants are common and not associated with adverse patient outcomes when variably present in the same lineage.

Background: Clostridium difficile ribotype-027, ribotype-078, and ribotype-017 are virulent and epidemic lineages. Trehalose metabolism variants in these ribotypes, combined with increased human trehalose consumption, have been hypothesised to have contributed to their emergence and virulence.

Methods: 5232 previously whole-genome sequenced C.

Omadacycline Gut Microbiome Exposure Does Not Induce Clostridium difficile Proliferation or Toxin Production in a Model That Simulates the Proximal, Medial, and Distal Human Colon.

A clinically reflective model of the human colon was used to investigate the effects of the broad-spectrum antibiotic omadacycline on the gut microbiome and the subsequent potential to induce simulated infection (CDI). Triple-stage chemostat gut models were inoculated with pooled human fecal slurry from healthy volunteers (age, ≥60 years). Models were challenged twice with 10 CFU spores (PCR ribotype 027).

New class of precision antimicrobials redefines role of S-layer in virulence and viability.

There is a medical need for antibacterial agents that do not damage the resident gut microbiota or promote the spread of antibiotic resistance. We recently described a prototypic precision bactericidal agent, Av-CD291.2, which selectively kills specific strains and prevents them from colonizing mice.

Lighting Up Clostridium Difficile: Reporting Gene Expression Using Fluorescent Lov Domains.

The uses of fluorescent reporters derived from green fluorescent protein have proved invaluable for the visualisation of biological processes in bacteria grown under aerobic conditions. However, their requirement for oxygen has limited their application in obligate anaerobes such as Clostridium difficile. Fluorescent proteins derived from Light, Oxygen or Voltage sensing (LOV) domains have been shown to bridge this limitation, but their utility as translational fusions to monitor protein expression and localisation in a strict anaerobic bacterium has not been reported.

Bacteriophage Combinations Significantly Reduce Clostridium difficile Growth In Vitro and Proliferation In Vivo.

The microbiome dysbiosis caused by antibiotic treatment has been associated with both susceptibility to and relapse of Clostridium difficile infection (CDI). Bacteriophage (phage) therapy offers target specificity and dose amplification in situ, but few studies have focused on its use in CDI treatment. This mainly reflects the lack of strictly virulent phages that target this pathogen.

LOV-based reporters for fluorescence imaging.

Chromophore-binding domains from plant and bacterial photoreceptor proteins have recently gathered increasing attention as new sources of genetically encoded fluorescent proteins (FPs). In particular, FPs based on the flavin-binding LOV (light, oxygen, or voltage sensing) domain offer advantages over green fluorescent protein (GFP) owing to their smaller size, pH and thermal stability, utility under anaerobic conditions and their ability to generate reactive oxygen species. This review focuses on the potential applications of this emerging class of fluorescent reporters, discusses the advantages and limitations of LOV-based FPs, whilst offering insights regarding the further development of this technology for bioimaging and photodynamic therapy.

The post-translational modification of the Clostridium difficile flagellin affects motility, cell surface properties and virulence.

Clostridium difficile is a prominent nosocomial pathogen, proliferating and causing enteric disease in individuals with a compromised gut microflora. We characterized the post-translational modification of flagellin in C. difficile 630.

The HtrA-like protease CD3284 modulates virulence of Clostridium difficile.

In the past decade, Clostridium difficile has emerged as an important gut pathogen. Symptoms of C. difficile infection range from mild diarrhea to pseudomembranous colitis.

Susceptibility of hamsters to Clostridium difficile isolates of differing toxinotype.

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ∼21,000 cases of AAD in 2011 in the U.K. alone.

Comprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals.

Chickens, pigs, and cattle are key reservoirs of Salmonella enterica, a foodborne pathogen of worldwide importance. Though a decade has elapsed since publication of the first Salmonella genome, thousands of genes remain of hypothetical or unknown function, and the basis of colonization of reservoir hosts is ill-defined. Moreover, previous surveys of the role of Salmonella genes in vivo have focused on systemic virulence in murine typhoid models, and the genetic basis of intestinal persistence and thus zoonotic transmission have received little study.

The anti-sigma factor TcdC modulates hypervirulence in an epidemic BI/NAP1/027 clinical isolate of Clostridium difficile.

Nosocomial infections are increasingly being recognised as a major patient safety issue. The modern hospital environment and associated health care practices have provided a niche for the rapid evolution of microbial pathogens that are well adapted to surviving and proliferating in this setting, after which they can infect susceptible patients. This is clearly the case for bacterial pathogens such as Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Enterococcus (VRE) species, both of which have acquired resistance to antimicrobial agents as well as enhanced survival and virulence properties that present serious therapeutic dilemmas for treating physicians.