Does Alkaline Colonic pH Predispose to Clostridium difficile Infection?

Gupta, Purba; Yakubov, Stanley; Tin, Kevin; Zea, Diego Javier; Garankina, Olga; Ghitan, Monica; Chapnick, Edward K.; Homel, Peter; Lin, Yu Shia; Koegel, Michael M

doi:10.14423/smj.0000000000000414

Cited by 16 publications

(17 citation statements)

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“…SCFAs are produced from dietary and hostderived carbohydrates, mainly by Lachnospiraceae and Ruminococcaceae, the families that were less abundant in CDI patients and carriers. They may have an effect on colonization resistance through reducing the luminal pH (and thereby creating an unfavorable environment for C. difficile) (44) and stimulating the defensive barrier, as one of the SCFAs (butyrate) is the main energy source of the gut epithelium (45,46). Amino acids may also play a role in susceptibility to C. difficile colonization, as they can enhance germination in the presence of secondary bile acids and may influence the immune system.…”

Section: Roles Of the Microbiotamentioning

confidence: 99%

Understanding Clostridium difficile Colonization

et al. 2018

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is the main causative agent of antibiotic-associated and health care-associated infective diarrhea. Recently, there has been growing interest in alternative sources of other than patients with infection (CDI) and the hospital environment. Notably, the role of -colonized patients as a possible source of transmission has received attention. In this review, we present a comprehensive overview of the current understanding of colonization. Findings from gut microbiota studies yield more insights into determinants that are important for acquiring or resisting colonization and progression to CDI. In discussions on the prevalence of colonization among populations and its associated risk factors, colonized patients at hospital admission merit more attention, as findings from the literature have pointed to their role in both health care-associated transmission of and a higher risk of progression to CDI once admitted. colonization among patients at admission may have clinical implications, although further research is needed to identify if interventions are beneficial for preventing transmission or overcoming progression to CDI.

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Section: Roles Of the Microbiotamentioning

confidence: 99%

Understanding Clostridium difficile Colonization

et al. 2018

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“…One possible mechanism for regulation of C. difficile susceptibility by SCFA is modulation of luminal pH. When concentrations of SCFAs decline, pH increases, resulting in an environment that is favorable for growth of Enterobacteriaceae and Clostridia, including C. difficile (103–105). …”

Section: Carbohydrate Fermentationmentioning

confidence: 99%

Structural and functional changes within the gut microbiota and susceptibility to Clostridium difficile infection

2016

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Alteration of the gut microbial community structure and function through antibiotic use increases susceptibility to colonization by Clostridium difficile and other enteric pathogens. However, the mechanisms that mediate colonization resistance remain elusive. As the leading definable cause of infectious diarrhea, toxigenic C. difficile represents a burden for patients and health care systems, underscoring the need for better diagnostics and treatment strategies. Next-generation sequence data has increased our understanding of how the gut microbiota is influenced by many factors including diet, disease, aging and drugs. However, a microbial-based biomarker differentiating C. difficile infection from antibiotic-associated diarrhea remains elusive. Metabolomics profiling, which is highly responsive to changes in physiological conditions, have shown promise in differentiating subtle disease phenotypes that exhibit a nearly identical microbiome community structure, suggesting metabolite-based biomarkers may be an ideal diagnostic for identifying patients with CDI. This review focuses on the current understanding of structural and functional changes to the gut microbiota during C. difficile infection obtained from studies assessing the microbiome and metabolome of samples from patients and murine models.

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“…The loss of function of NHE3 by toxin B of C. difficile caused an altered intestinal environment with an increase in the luminal and fecal pH (23). A further cohort study reported a strong association between a more alkaline fecal pH and CDI, suggesting that higher pH in the GI tract may influence disease symptoms (24).…”

Section: Introductionmentioning

confidence: 99%

The impact of pH onClostridioides difficilesporulation and physiology

Wetzel

McBride

2019

Preprint

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23 24 25 2 ABSTRACT 26Clostridioides difficile is a pathogenic bacterium that infects the human colon to cause 27 diarrheal disease. Growth of the bacterium is known to be dependent on certain bile 28 acids, oxygen levels and nutrient availability in the intestine, but how the environmental 29 pH can influence C. difficile is mostly unknown. Previous studies indicated that C. difficile 30 modulates the intestinal pH, and prospective cohort studies have found a strong 31 association between a more alkaline fecal pH and C. difficile infection. Based on these 32 data we hypothesized that C. difficile physiology can be affected by various pH 33 conditions. In this study, we investigated the impact of a range of pH conditions on 34 C. difficile to assess potential effects on growth, sporulation, motility and toxin production 35 in the strains 630∆erm and R20291. We observed pH-dependent differences in 36 sporulation rate, spore morphology and viability. Sporulation frequency was lowest under 37 acidic conditions, and differences in cell morphology were apparent at low pH. In alkaline 38 environments, C. difficile sporulation was greater for strain 630∆erm, whereas R20291 39 produced relatively high levels of spores in a broad range of pH conditions. Rapid 40 changes in pH during exponential growth impacted sporulation similarly among the 41 strains. Furthermore, we observed an increase in C. difficile motility with increases in pH, 42and strain-dependent differences in toxin formation under acidic conditions. The data 43 demonstrate that pH is an important parameter that affects C. difficile physiology and 44 may reveal relevant insights into the growth and dissemination of this pathogen. 45 46 47 IMPORTANCE 48 Clostridioides difficile is an anaerobic bacterium that causes gastrointestinal disease. C.49 difficile forms dormant spores, which can survive harsh environmental conditions, 50 allowing their spread to new hosts. In this study, we determine how intestinally relevant 51 3 pH conditions impact C. difficile physiology in the two divergent strains, 630∆erm and 52 R20291. Our data demonstrate that low pH conditions reduce C. difficile growth, 53 sporulation, and motility. However, toxin formation and spore morphology are 54 differentially impacted in the strains at low pH. In addition, we observed that alkaline 55 environments reduced C. difficile growth, but increased cell motility. When pH was 56 adjusted rapidly during growth, we observed similar impacts on both strains. This study 57 provides new insights into the phenotypic diversity of C. difficile grown under the diverse 58 pH conditions present in the intestinal tract, and demonstrates similarities and 59 differences in the pH responses of different C. difficile isolates. 60 61 62 INTRODUCTION 63 Clostridioides difficile is an emerging gastrointestinal pathogen, which often infects 64 patients who have recently received antibiotics. Upon ingestion, the dormant spores 65 survive the acidic pH of the stomach and enter the small intestine, where primary bile ...

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Does Alkaline Colonic pH Predispose to Clostridium difficile Infection?

Abstract: A strong association between C. difficile infection and alkaline stool pH was found.

Cited by 16 publications

References 1 publication

Understanding Clostridium difficile Colonization

Understanding Clostridium difficile Colonization

Structural and functional changes within the gut microbiota and susceptibility to Clostridium difficile infection

The impact of pH onClostridioides difficilesporulation and physiology

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