Enteric dysbiosis and fecal calprotectin expression in premature infants

Abstract

Background: Premature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC). Methods: Stool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks’ postnatal age. Fecal microbiome was surveyed using PCR-amplification of the V4 region of 16S rRNA, and FC was measured by enzyme immunoassay. Results: We enrolled 45 VLBW infants (gestation 27.9±2.2 weeks, birth weight 1126±208 g) and obtained stool samples at 9.9±3, 20.7±4.1, and 29.4±4.9 days. FC was positively correlated with the genus Klebsiella ( r = 0.207, p = 0.034) and its dominant amplicon sequence variant ( r = 0.290, p = 0.003) but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance. Conclusion: In premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella , and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution.

Impact of Probiotic B. Infantis EVC001 Feeding in Premature Infants on the Gut Microbiome, Nosocomially Acquired Antibiotic Resistance, and Enteric Inflammation

“…Enterobacteriaceae is consistent with examples of preterm infant gut microbiome development in the literature [47,48], with taxa-dependent implications for preterm infant morbidity and development [4,10,45]. Among preterm infants fed EVC001, we observed that novel microbiome compositions developed, where colonization by B. infantis resulted in the displacement of bacteria associated with increased risk of preterm morbidities [5](e.g.…”

“…These services include increased availability of nutrients from human milk, improved maturation of the intestinal epithelium, reduced enteric inflammation, and mitigated risk of infection in hospitalized infants [3,21,43,44,46]. In this study, we found preterm infants in two hospitals were colonized by nosocomially acquired bacteria despite a human milk diet, and the resulting gut microbiomes, absent intervention with B. infantis EVC001, developed comparably to reports in the literature on the preterm infant gut microbiome [1,2,10]. Early acquisition of skin-derived bacteria (e.g.…”

“…Gut microbiome composition has previously been shown to modulate the enteric inflammatory markers in term and preterm infants [10,16]. Moreover, the hospital feeding protocol continued feeding of B. infantis EVC001 up to 34 weeks cGA (see Methods).…”

“…These bacteria confer negative impacts on neonatal growth and development [1] and are associated with an increased risk of necrotizing enterocolitis (NEC) [4,5] and lateonset sepsis [6][7][8]. Importantly, increased prevalence of Proteobacteria has been shown to precede NEC [4,8,9] and exacerbate enteric inflammation [10]. Proteobacteria, broadly, have also been associated with the pathogenesis of sepsis and NEC in premature infants [11][12][13].…”

Targeted inhibition of thrombin attenuates murine neonatal necrotizing enterocolitis

“…inflammation | intestinal | coagulation N ecrotizing enterocolitis (NEC) is an idiopathic, inflammatory bowel necrosis of premature infants and a leading cause of mortality in infants born between 22 and 28 wk of gestation (1)(2)(3). Premature infants who develop bacterial overgrowth and dysbiosis with a predominance of Gram-negative bacteria in their enteric microenvironment may be at enhanced risk of NEC (4)(5)(6). This risk of NEC may increase further upon exposure to environmental insults such as hypoxia and/or hypothermia, inadequate mucosal antimicrobial defenses due to immature Paneth cells, inflammation in the anemic intestine following red-blood-cell transfusions, or following enteral exposure to immunological stimulants (6)(7)(8)(9)(10).…”