Environmentally Acquired Bacillus and Their Role in C. difficile Colonization Resistance

Ferreira, William T.; Hong, Huynh A.; Adams, James R. G.; Hess, Mateusz; Kotowicz, Natalia; Tan, Sisareuth; Ferrari, Enrico; Brisson, Alain; Zentek, Jürgen; Soloviev, Mikhail; Cutting, Simon M.

doi:10.3390/biomedicines10050930

Cited by 3 publications

(1 citation statement)

References 83 publications

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“…Spores are members of the aerobiome and also found in soil and vegetation 39,40 . As such animals and humans are exposed to a low level of Bacillus on a daily basis 41,42 . Considered together, the use of bacterial spores as oral vaccine vehicles is compelling.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic immunization to Helicobacter pylori infection using spore vectored vaccines

et al. 2023

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Helicobacter pylori (HP) is a Gram-negative human pathogenic bacterium believed to be carried by an estimated 50% of the world's population. 1 Infection typically occurs in childhood and if untreated an individual will likely remain colonized for life. 2 Of those infected about 15% may go on to develop pathological symptoms, typically chronic gastritis and peptic ulcer disease (gastric and duodenal ulceration) with the potential for gastric cancer (adenocarcinoma and lymphoma). H. pylori infection is thought to be linked with more than 90% of gastric cancers and normally results if the infection is left untreated. 3 Gastric adenocarcinoma is now the 5th most common cancer and the 3rd in terms of cancer-related deaths. Unfortunately, by the time gastric cancer has developed it is nearly impossible to

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Section: Discussionmentioning

confidence: 99%

Prophylactic immunization to Helicobacter pylori infection using spore vectored vaccines

et al. 2023

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A Family of Cyclic Lipopeptides Found in Human Isolates of Bacillus Ameliorates Acute Colitis via Direct Agonism of Toll-Like Receptor 2 in a Murine Model of Inflammatory Bowel Disease

Horwell,

Vittoria,

Hong

et al. 2024

Dig Dis Sci

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Background The Bacillus -derived cyclic lipopeptides (surfactin, iturin, and fengycin) form potent He terogeneous L ipopeptide M icelle (HeLM) complexes. HeLM is a small molecule that has been shown to have immunomodulatory effects. However, how HeLM regulates inflammation is not clear, moreover its application to Inflammatory Bowel Disease (IBD), specifically Ulcerative Colitis (UC), has not been tested before. Aims To use a murine model of IBD and determine the effects of HeLM and related molecular mechanisms of action. Methods Colitis was induced in mice by administration of 4% Dextran Sodium Sulfate. Three preparations were tested against negative and positive controls: Purified HeLM, the wild-type strain that produces it, and an isogenic mutant that does not produce HeLM. Clinical, biochemical, and histological scoring systems were used to assess the severity of colitis. RT-qPCR and cell cultures were used to determine the levels of molecular signaling. Fecal samples were processed for metagenomic analysis. Results Purified HeLM, and the wild-type strain, significantly decreased the severity of colitis as determined by the disease activity index (DAI), mouse colitis histology index (MCHI), fecal calprotectin, and colonic length. This effect was not seen in the mutant. HeLM was found to be an agonist to TLR-2, seemingly activating the Toll-Like Receptor 2/IL-10 pathway, with subsequent downregulation of inflammatory cytokines (TNF-α, IL-1β, and IL-6). At higher concentrations HeLM inhibited lipopolysaccharide ligands from activating TLR-4. The reduction in colitis was not due to microbiome modulation, as had previously been hypothesized. Conclusion Our results indicate that HeLM ameliorates colitis by TLR-2-induced IL-10 production and possibly via the inhibition of lipopolysaccharide. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-024-08534-2.

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Modelling a Western Lifestyle in Mice: A Novel Approach to Eradicating Aerobic Spore-Forming Bacteria from the Colonic Microbiome and Assessing Long-Term Clinical Outcomes

Horwell,

Ferreira,

Hong

et al. 2024

Biomedicines

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Introduction: The environmentally acquired aerobic spore-forming (EAS-Fs) bacteria that are ubiquitous in nature (e.g., soil) are transient colonisers of the mammalian gastro-intestinal tract. Without regular exposure, their numbers quickly diminish. These species of bacteria have been suggested to be essential to the normal functioning of metabolic and immunogenic health. The modern Western lifestyle restricts exposure to these EAS-Fs, possibly explaining part of the pathogenesis of many Western diseases. To date, the only animal studies that address specific microbiome modelling are based around germ-free animals. We have designed a new animal model that specifically restricts exposure to environmental sources of bacteria. Methodology: A new protocol, termed Super Clean, which involves housing mice in autoclaved individually ventilated cages (IVCs), with autoclaved food/water and strict ascetic handling practice was first experimentally validated. The quantification of EAS-Fs was assessed by heat-treating faecal samples and measuring colony-forming units (CFUs). This was then compared to mice in standard conditions. Mice were housed in their respective groups from birth until 18 months. Stool samples were taken throughout the experiment to assess for abundance in transiently acquired environmental bacteria. Clinical, biochemical, histological, and gene expression markers were analysed for diabetes, hypercholesterolaemia, obesity, inflammatory bowel disease, and non-alcoholic fatty liver disease (the “diseases of the West”). Results: Our results show that stringent adherence to the Super Clean protocol produces a significantly decreased abundance of aerobic spore-forming Bacillota after 21 days. This microbiomic shift was correlated with significantly increased levels of obesity and impaired glucose metabolism. There was no evidence of colitis, liver disease or hypercholesterolaemia. Conclusions: This new murine model successfully isolates EAS-Fs and has potential utility for future research, allowing for an investigation into the clinical impact of living in relative hygienic conditions.

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Environmentally Acquired Bacillus and Their Role in C. difficile Colonization Resistance

Cited by 3 publications

References 83 publications

Prophylactic immunization to Helicobacter pylori infection using spore vectored vaccines

Prophylactic immunization to Helicobacter pylori infection using spore vectored vaccines

A Family of Cyclic Lipopeptides Found in Human Isolates of Bacillus Ameliorates Acute Colitis via Direct Agonism of Toll-Like Receptor 2 in a Murine Model of Inflammatory Bowel Disease

Modelling a Western Lifestyle in Mice: A Novel Approach to Eradicating Aerobic Spore-Forming Bacteria from the Colonic Microbiome and Assessing Long-Term Clinical Outcomes

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