Impact of early-life events on the susceptibility to Clostridium difficile colonisation and infection in the offspring of the pig

Abstract

Clostridium difficile has been documented as a major cause of uncontrolled outbreaks of enteritis in neonatal pigs and antibiotic-associated infections in clinical settings. It belongs to the natural cohort of early colonisers of the gastrointestinal tract of pigs and can be detected in faeces up to two weeks post-partum. In older pigs, it often remains under the detection limit. Most neonatal pigs show no clinical signs of disease although C. difficile and its toxins can be detected at high levels in faeces. Increased mortality rates associated with C. difficile on pig farms are, so far, considered "spontaneous" and the predisposing factors are mostly not defined. The infection caused by C. difficile is multifactorial and it is likely that the repertoire of maternal factors, host physiology, the individually developing gut microbiota, co-infections and environmental stress define the conditions for disease development. In this addendum to our recently published work on CDI in neonatal piglets, we discuss the "early-life events" that influence C. difficile spread and infection in neonatal piglets.

Porcine Colostrum Protects the IPEC-J2 Cells and Piglet Colon Epithelium against Clostridioides (syn. Clostridium) difficile Toxin-Induced Effects

“…In addition, we combined the porcine colostrum together with C. difficile toxins to study whether the porcine colostrum would show any evidence of protection from cell intoxication. Here, the toxins drastically reduced IPEC-J2 cell integrity, similar to previous observations [5]. In addition, the presence of toxins led to a slightly lower gene expression ratios of TJ proteins, immune markers and finally to cell death.…”

“…The late colostrum was obtained from four lactating sows one day post-partum and stored frozen at −30 • C until further analyses. The presence of IgG anti-toxin A antibodies was previously confirmed by immunoassay [5].…”

“…Previously performed tests showed that a two-hour incubation at a toxin concentration of 13 ng/mL of TcdA and 8 ng/mL of TcdB was suitable to demonstrate detrimental changes in IPEC-J2 cells by lowering the TEER values within time but without inducing prominent cell damage or death (light microscopic evaluation), so that further manipulations such as cell washing could be performed without loss of the cells. A one-fold higher concentration of the toxins or a longer incubation time led to a drastic fall in TEER [5], as well as disintegration and break-up of the cells, which could be seen under a light microscope. In addition, previous preliminary tests showed that slight variations of the established toxin concentration had only a small impact on the TEER values.…”

“…Their action is related to the modulation of the intestinal epithelial cell physiology and disruption 2 of 14 of barrier function via inactivation of Rho proteins involved in the formation of the cytoskeleton. This leads to disruption of tight junction (TJ) proteins and finally to a loss of epithelial integrity, as demonstrated in porcine and human cell lines [4][5][6][7]. Such a scenario of events may lead to the typical signs of C. difficile infection (CDI) [8,9] with severe consequences, such as animal death or growth retardation in piglets that survived the infection [10].…”

Gut microbiome features associated withClostridium difficilecolonization in puppies

“…The role of the commensal gut microbiota in C. difficile colonization resistance has been demonstrated in people (15–19) and in certain species of animals (20–22). Human subject and animal model studies suggest key microbiome features, including community diversity and specific taxa, are involved in protection against C. difficile .…”