Natural Clostridioides difficile Toxin Immunization in Colonized Infants

Abstract

Background Clostridioides (Clostridium) difficile colonization is common among infants. Serological sequelae of infant C. difficile colonization are poorly understood. Methods In this prospective cohort study of healthy infants, stools serially collected between ages 1-2 and 9-12 months were tested for non-toxigenic and toxigenic C. difficile (TCD). Cultured isolates underwent whole-genome sequencing. Serum collected at 9–12 months underwent measurement of IgA, IgG, and IgM against TCD toxins A and B and neutralizing antibody (NAb) titers against toxin B. For comparison, antitoxin IgG and NAb were measured in cord blood from 50 mothers unrelated to study infants. Results Among 32 infants, 16 (50%) were colonized with TCD; 12 were first colonized >1 month before serology measurements. A variety of sequence types were identified, and there was evidence of putative in-home (enrolled siblings) and outpatient clinic transmission. Infants first colonized with TCD >1 month prior had significantly greater serum antitoxin IgA and IgG against toxins A (P = .02 for both) and B (P = .009 and .008, respectively) compared with non–TCD-colonized infants, and greater IgG compared with unrelated cord blood (P = .005). Five of 12 (42%) colonized infants had detectable NAb titers compared with zero non–TCD-colonized infants (P = .02). Breastfeeding was not associated with differences in serological measurements. Conclusions TCD colonization is associated with a humoral immune response against toxins A and B, with evidence of toxin B neutralization in vitro. The extent and duration of protection against CDI later in life afforded by natural C. difficile immunization events require further investigation.

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

“…In this context, our findings strongly support the important role of maternal protection against CDI in neonatal piglets. Although C. difficile outgrowth in pigs as well as in humans seems to be dependent on the microbial diversity [46,47], piglets colonised by toxigenic C. difficile may also be able to further develop immunity against toxins, similar to human infants [48], protecting the gut from potential intoxication and infection in the future.…”

<i>C. difficile</i>-infection and microbyota in newborns: resolved and outstanding issues

“…Существует бимодальное распределение заболеваемости C. difficile-инфекцией в детском возрасте с пиками в раннем детстве и в позднем подростковом возрасте [86,87]. На основании исследования гуморального ответа есть предположение, что «естественная иммунизация» токсинами А и В (TcdA/TcdB) в младенчестве на фоне колонизации токсигенными штаммами C. difficile может защищать от C. difficile-инфекции до позднего подросткового возраста за счет высокого титра нейтрализующих антител IgA, IgG к токсину B [88]. Однако эта гипотеза требует дальнейшего изучения.…”

From Nursery to Nursing Home: Emerging Concepts in Clostridioides difficile Pathogenesis

“…Moreover, higher concentrations of IgA in breastfed infants can serve as a potent toxin A neutralizer (51,52). In fact, a recent serological analysis of infants colonized with toxigenic strains of C. difficile revealed modest IgA and IgG response to toxins A and B, which could affect protection against infection later in life (53).…”