Interplay between inflammatory bowel disease therapeutics and the gut microbiome reveals opportunities for novel treatment approaches.

Inflammatory bowel disease (IBD) is a complex heterogeneous disorder defined by recurring chronic inflammation of the gastrointestinal tract, attributed to a combination of factors including genetic susceptibility, altered immune response, a shift in microbial composition/microbial insults (infection/exposure), and environmental influences. Therapeutics generally used to treat IBD mainly focus on the immune response and include non-specific anti-inflammatory and immunosuppressive therapeutics and targeted therapeutics aimed at specific components of the immune system. Other therapies include exclusive enteral nutrition and emerging stem cell therapies.

Novel, non-colonizing, single-strain live biotherapeutic product ADS024 protects against infection challenge .

Background: The Centers for Disease Control and Prevention estimate that () causes half a million infections (CDI) annually and is a major cause of total infectious disease death in the United States, causing inflammation of the colon and potentially deadly diarrhea. We recently reported the isolation of ADS024, a () strain, which demonstrated direct bactericidal activity against , with minimal collateral impact on other members of the gut microbiota. In this study, we hypothesized that activities of ADS024 will translate to protect against CDI challenge in mouse models.

Modulation of the gut microbiome with nisin.

Nisin is a broad spectrum bacteriocin used extensively as a food preservative that was identified in Lactococcus lactis nearly a century ago. We show that orally-ingested nisin survives transit through the porcine gastrointestinal tract intact (as evidenced by activity and molecular weight determination) where it impacts both the composition and functioning of the microbiota. Specifically, nisin treatment caused a reversible decrease in Gram positive bacteria, resulting in a reshaping of the Firmicutes and a corresponding relative increase in Gram negative Proteobacteria.

Identification of ADS024, a newly characterized strain of Bacillus velezensis with direct Clostridiodes difficile killing and toxin degradation bio-activities.

Clostridioides difficile infection (CDI) remains a significant health threat worldwide. C. difficile is an opportunistic, toxigenic pathogen that takes advantage of a disrupted gut microbiome to grow and produce signs and symptoms ranging from diarrhea to pseudomembranous colitis.

Impact of nisin on Clostridioides difficile and microbiota composition in a faecal fermentation model of the human colon.

Aims: Nisin is a bacteriocin with a broad spectrum of activity against Gram-positive bacteria. The aims were to assess nisin activity against Clostridioides difficile in a complex microbial environment and determine the minimum inhibitory concentration at which C. difficile growth is suppressed whilst having minimal impact on the faecal microbiota.

The microbiome of deep-sea fish reveals new microbial species and a sparsity of antibiotic resistance genes.

Adaptation to life in the deep-sea can be dramatic, with fish displaying behaviors and appearances unlike those seen in any other aquatic habitat. However, the extent of which adaptations may have developed at a microbial scale is not as clear. Shotgun metagenomic sequencing of the intestinal microbiome of 32 species of deep-sea fish from across the Atlantic Ocean revealed that many of the associated microbes differ extensively from those previously identified in reference databases.

A multicentre analysis of Clostridium difficile in persons with Cystic Fibrosis demonstrates that carriage may be transient and highly variable with respect to strain and level.

Purpose: Clostridium difficile has been reported to occur in the gastrointestinal tract of 50% of Cystic Fibrosis (CF) subjects, however, clinical C. difficile infection (CDI) is a rare occurrence in this cohort despite the presence of toxigenic and hypervirulent ribotypes. Here, we present the first longitudinal, multicentre analysis of C.

Protecting the outside: biological tools to manipulate the skin microbiota.

Interest surrounding the role that skin microbes play in various aspects of human health has recently experienced a timely surge, particularly among researchers, clinicians and consumer-focused industries. The world is now approaching a post-antibiotic era where conventional antibacterial therapeutics have shown a loss in effectiveness due to overuse, leading to the looming antibiotic resistance crisis. The increasing threat posed by antibiotic resistance is compounded by an inadequate discovery rate of new antibiotics and has, in turn, resulted in global interest for alternative solutions.

Encapsulated cyclosporine does not change the composition of the human microbiota when assessed and .

Management of steroid-refractory ulcerative colitis has predominantly involved treatment with systemic cyclosporine A (CyA) and infliximab. The purpose of this study was to assess the effect of using a colon-targeted delivery system CyA formulation on the composition and functionality of the gut microbiota. faecal fermentations from six healthy control subjects were treated with coated minispheres (SmPill) with (+) or without (-) CyA and compared with a non-treated control in a model colon system.

Nisin J, a Novel Natural Nisin Variant, Is Produced by Staphylococcus capitis Sourced from the Human Skin Microbiota.

The skin microbiota is thought to play a key role in host protection from infection. Nisin J is a novel nisin variant produced by APC 2923, a strain isolated from the toe web space area in a screening study performed on the human skin microbiota. Whole-genome sequencing and mass spectrometry of the purified peptide confirmed that APC 2923 produces a 3,458-Da bacteriocin, designated nisin J, which exhibited antimicrobial activity against a range of Gram-positive pathogens, including methicillin-resistant (MRSA) and The gene order in the nisin J gene cluster () differs from that of other nisin variants in that it is lacking the nisin regulatory genes, , as well as the nisin immunity gene Nisin J has 9 amino acid changes compared to prototypical nisin A, with 8 amino acid substitutions, 6 of which are not present in other nisin variants (Ile4Lys, Met17Gln, Gly18Thr, Asn20Phe, Met21Ala, Ile30Gly, Val33His, and Lys34Thr), and an extra amino acid close to the C terminus, rendering nisin J the only nisin variant to contain 35 amino acids.

A Live Bio-Therapeutic for Mastitis, Containing DPC3147 With Comparable Efficacy to Antibiotic Treatment.

Bovine mastitis is an ongoing significant concern in the dairy and agricultural industry resulting in substantial losses in milk production and revenue. Among the predominant etiological agents of bovine mastitis are , , and Currently, the treatment of choice for bovine mastitis involves the use of commercial therapeutic antibiotic formulations such as Terrexine, containing both kanamycin and cephalexin. Such antibiotics are regularly administered in more than one dose resulting in the withholding of milk for processing for a number of days.

Draft Genome Sequence of Bacillus thuringiensis DPC6431, Producer of the Bacteriocin Thuricin CD.

We report the draft genome sequence of DPC6431, a producer of the anticlostridial bacteriocin thuricin CD and isolated from a human fecal sample. The assembly comprises 96 contigs for a total of 5,581,839 bp, with 32.5% G+C content.

APC 678 Reduces Shedding of the Pathogen in a Murine Model.

is a common cause of health-care acquired diarrhea, resulting in a spectrum of disease from mild diarrhea to life-threatening illness. Sixty strains were screened for anti- activity using a co-culture method. Based on their ability to inhibit , APC 678 and DPC 6111 were selected for study in a murine model of infection.

Effects of a polysaccharide-rich extract derived from Irish-sourced Laminaria digitata on the composition and metabolic activity of the human gut microbiota using an in vitro colonic model.

Background: Brown seaweeds are known to be a rich source of fiber with the presence of several non-digestible polysaccharides including laminarin, fucoidan and alginate. These individual polysaccharides have previously been shown to favorably alter the gut microbiota composition and activity albeit the effect of the collective brown seaweed fiber component on the microbiota remains to be determined.

Methods: This study investigated the effect of a crude polysaccharide-rich extract obtained from Laminaria digitata (CE) and a depolymerized CE extract (DE) on the gut microbiota composition and metabolism using an in vitro fecal batch culture model though metagenomic compositional analysis using 16S rRNA FLX amplicon pyrosequencing and short-chain fatty acid (SCFA) analysis using GC-FID.

Human skin microbiota is a rich source of bacteriocin-producing staphylococci that kill human pathogens.

The demand for novel antimicrobial therapies due to the threat posed by antimicrobial resistance has resulted in a growing interest in the protective role of our skin bacteria and the importance of competition among bacteria on the skin. A survey of the cultivable bacteria on human skin was undertaken to identify the capacity of the skin microbiota to produce bacteriocins with activity against skin pathogens. Twenty-one bacteriocins produced by bacteria isolated from seven sites on the human body of each subject exhibited inhibition spectra ranging from broad to narrow range, inhibiting many Gram-positive bacteria, including opportunistic skin pathogens such as Propionibacterium acnes (recently renamed Cutibacterium acnes), Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus (MRSA).

Protecting bactofencin A to enable its antimicrobial activity using mesoporous matrices.

There is huge global concern surrounding the emergence of antimicrobial resistant bacteria and this is resulting in an inability to treat infectious diseases. This is due to a lack of new antimicrobials coming to the market and irresponsible use of traditional antibiotics. Bactofencin A, a novel antimicrobial peptide which shows potential as an antibiotic, is susceptible to enzyme degradation.

Genus-Wide Assessment of Antibiotic Resistance in spp.

species are widely used as probiotics and starter cultures for a variety of foods, supported by a long history of safe usage. Although more than 35 species meet the European Food Safety Authority (EFSA) criteria for qualified presumption of safety status, the safety of species and their carriage of antibiotic resistance (AR) genes is under continuing review. To comprehensively update the identification of AR in the genus , we determined the antibiotic susceptibility patterns of 182 type strains and compared these phenotypes to their genotypes based on genome-wide annotations of AR genes.

Delivery of a hydrophobic drug into the lower gastrointestinal system via an endogenous enzyme-mediated carrier mechanism: An in vitro study.

Clofazimine (CFZ) is a hydrophobic antibiotic agent which exhibits poor solubility. This poor solubility was overcome herein by the formulation of CFZ with the digestive enzyme pepsin. It is shown that pepsin can actively bind 11 CFZ molecules in the protein's native gastric environment, forming a CFZ-pepsin complex.

The Use of a Mini-Bioreactor Fermentation System as a Reproducible, High-Throughput Batch Model of the Distal Colon.

colon fermentation systems are highly versatile as models for analyzing gastrointestinal tract microbiota composition and functionality. colon models range in size and functionality from bench-top micro fermenters to large units housed in individualized cabinets. The length of set-up time (including stabilization periods) for each fermentation system can range from hours to weeks to months.

Heterologous Expression of Biopreservative Bacteriocins With a View to Low Cost Production.

Bacteriocins, a heterogenous group of antibacterial ribosomally synthesized peptides, have potential as bio-preservatives in in a wide range of foods and as future therapeutics for the inhibition of antibiotic-resistant bacteria. While many bacteriocins have been characterized, several factors limit their production in large quantities, a requirement to make them commercially viable for food or pharma applications. The identification of new bacteriocins by database mining has been promising, but their potential is difficult to evaluate in the absence of suitable expression systems.

Evaluation of the Potential of Adjuncts for Flavor Compounds Development and Diversification in Short-Aged Cheddar Cheese.

The non-starter microbiota of Cheddar cheese mostly comprises mesophilic lactobacilli, such as , and . These bacteria are recognized for their potential to improve Cheddar cheese flavor when used as adjunct cultures. In this study, three strains of (DPC2071, DPC4206, and DPC4536) were evaluated for their contribution to the enhancement and diversification of flavor in short-aged Cheddar cheese.

Reincarnation of Bacteriocins From the Pangenomic Graveyard.

Bacteria commonly produce narrow spectrum bacteriocins as a means of inhibiting closely related species competing for similar resources in an environment. The increasing availability of genomic data means that it is becoming easier to identify bacteriocins encoded within genomes. Often, however, the presence of bacteriocin genes in a strain does not always translate into biological antimicrobial activity.

Oral Delivery of Nisin in Resistant Starch Based Matrices Alters the Gut Microbiota in Mice.

There is a growing recognition of the role the gastrointestinal microbiota plays in health and disease. Ingested antimicrobial proteins and peptides have the potential to alter the gastrointestinal microbiota; particularly if protected from digestion. Nisin is an antimicrobial peptide that is used as a food preservative.

Fighting biofilms with lantibiotics and other groups of bacteriocins.

Biofilms are sessile communities of bacteria typically embedded in an extracellular polymeric matrix. Bacterial cells embedded in biofilms are inherently recalcitrant to antimicrobials, compared to cells existing in a planktonic state, and are notoriously difficult to eradicate once formed. Avenues to tackle biofilms thus far have largely focussed on attempting to disrupt the initial stages of biofilm formation, including adhesion and maturation of the biofilm.