Microbiota-targeted maternal antibodies protect neonates from enteric infection

Zheng, Wenfeng; Zhao, Wenjing; Wu, Meng; Song, Xiaohe; Caro, Florence; Sun, Ximei; Gazzaniga, Francesca S.; Stefanetti, Giuseppe; Oh, Sungwhan F.; Mekalanos, John J.; Kasper, Dennis L.

doi:10.1038/s41586-019-1898-4

Cited by 104 publications

(119 citation statements)

References 44 publications

(44 reference statements)

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“…This suggests that donor milk may be inferior to maternal milk in an immunological capacity only, retaining qualities sufficient to influence C. perfringens colonisation patterns in some contexts. It has recently been demonstrated that neonatal mice can be protected from enteric infection by antibodies delivered through breast milk [39]. The absence of competing milk commensals in donor milk may perhaps further explain why in our study it failed to influence C. perfringens carriage in the way that maternal milk did.…”

Section: Discussionmentioning

confidence: 55%

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

et al. 2020

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Background: Clostridium perfringens forms part of the human gut microbiota and has been associated with lifethreatening necrotising enterocolitis (NEC) in premature infants. Whether specific toxigenic strains are responsible is unknown, as is the extent of diversity of strains in healthy premature babies. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains. Methods: C. perfringens was isolated by culture from faecal samples from 333 infants and their toxin gene profiles analysed by PCR. A survival analysis was used to identify factors affecting probability of carriage. Competitive growth experiments were used to explore the results of the survival analysis. Results: 29.4% of infants were colonized with C. perfringens before they left hospital. Three factors were inversely associated with probability of carriage: increased duration of maternal milk feeds, CPAP oxygen treatment and antibiotic treatment. C. perfringens grew poorly in breast milk and was significantly outperformed by Bifidobacterium infantis, whether grown together or separately. Toxin gene screening revealed that infants carried isolates positive for collagenase, perfringolysin O, beta 2, beta, becA/B, netB and enterotoxin toxin genes, yet none were observed to be associated with the development of NEC. Conclusions: Approximately a third of preterm infants are colonised 3 weeks after birth with toxin gene-carrying C. perfringens. We speculate that increased maternal breast milk, oxygen and antibiotic treatment creates an environment in the gut hostile to growth of C. perfringens. Whilst potentially toxigenic C. perfringens isolates were frequent, no toxin type was associated with NEC. Trial registration: clinicaltrials.gov NCT01102738, registered 13th April 2010.

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Section: Discussionmentioning

confidence: 55%

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

et al. 2020

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“…Infections are also prevented indirectly by NAb binding self-receptors such as CCR5, essential for the entry of the HIV virions (158). Maternal natural IgG antibodies protected neonatal mice from infection with enterotoxigenic E. coli infections when these antibodies were delivered across the placenta or through milk (159).…”

Section: Natural Antibodies Against Pathogens and Infectionsmentioning

confidence: 99%

Current Understanding of Natural Antibodies and Exploring the Possibilities of Modulation Using Veterinary Models. A Review

2020

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Natural antibodies (NAb) are defined as germline encoded immunoglobulins found in individuals without (known) prior antigenic experience. NAb bind exogenous (e.g., bacterial) and self-components and have been found in every vertebrate species tested. NAb likely act as a first-line immune defense against infections. A large part of NAb, so called natural autoantibodies (NAAb) bind to and clear (self) neo-epitopes, apoptotic, and necrotic cells. Such self-binding antibodies cannot, however, be considered as pathogenic autoantibodies in the classical sense. IgM and IgG NAb and NAAb and their implications in health and disease are relatively well-described in humans and mice. NAb are present in veterinary (and wildlife) species, but their relation with diseases and disorders in veterinary species are much less known. Also, there is little known of IgA NAb. IgA is the most abundant immunoglobulin with essential pro-inflammatory and homeostatic properties urging for more research on the importance of IgA NAb. Since NAb in humans were indicated to fulfill important functions in health and disease, their role in health of veterinary species should be investigated more often. Furthermore, it is unknown whether levels of NAb-isotypes and/or idiotypes can and should be modulated. Veterinary species as models of choice fill in a niche between mice and (non-human) primates, and the study of NAb in veterinary species may provide valuable new insights that will likely improve health management. Below, examples of the involvement of NAb in several diseases in mostly humans are shown. Possibilities of intravenous immunoglobulin administration, targeted immunotherapy, immunization, diet, and genetic modulation are discussed, all of which could be well-studied using animal models. Arguments are given why veterinary immunology should obtain inspiration from human studies and why human immunology would benefit from veterinary models. Within the One Health concept, findings from veterinary (and wildlife) studies can be related to human studies and vice versa so that both fields will mutually benefit. This will lead to a better understanding of NAb: their origin, activation mechanisms, and their implications in health and disease, and will lead to novel health management strategies for both human and veterinary species.

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“…This suggests that donor milk may be inferior to maternal milk in an immunological capacity only, retaining qualities sufficient to influence C. perfringens colonisation patterns in some contexts. It has recently been demonstrated that neonatal mice can be protected from enteric infection by antibodies delivered through breast milk (39). The absence of competing milk commensals in donor milk may perhaps further explain why in our study it failed to influence C.…”

Section: Discussionmentioning

confidence: 60%

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

Shaw

Cornwell

Sim

et al. 2020

Preprint

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Background Clostridium perfringens forms part of the human gut microbiota and has been associated with life-threatening necrotising enterocolitis (NEC) in premature infants. Whether specific toxigenic strains are responsible is unknown, as is the extent of diversity of strains in healthy premature babies. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains. Methods C. perfringens was isolated by culture from faecal samples from 333 infants and their toxin gene profiles analysed by PCR. A survival analysis was used to identify factors affecting probability of carriage. Competitive growth experiments were used to explore the results of the survival analysis. Results 29.4% of infants were colonized with C. perfringens before they left hospital. Three factors were inversely associated with probability of carriage: increased duration of maternal milk feeds, CPAP oxygen treatment and antibiotic treatment. C. perfringens grew poorly in breast milk and was significantly outperformed by Bifidobacterium infantis, whether grown together or separately. Toxin gene screening revealed that infants carried isolates positive for collagenase, perfringolysin O, beta 2, beta, becA/B, netB and enterotoxin toxin genes, yet none were observed to be associated with the development of NEC. Conclusions Approximately a third of preterm infants are colonised three weeks after birth with toxin gene-carrying C. perfringens. We speculate that increased maternal breast milk, oxygen and antibiotic treatment creates an environment in the gut hostile to growth of C. perfringens. Whilst potentially toxigenic C. perfringens isolates were frequent, no toxin type was associated with NEC.

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Microbiota-targeted maternal antibodies protect neonates from enteric infection

Cited by 104 publications

References 44 publications

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

Current Understanding of Natural Antibodies and Exploring the Possibilities of Modulation Using Veterinary Models. A Review

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

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