Gut microbiota in neonates with congenital gastrointestinal surgical conditions: a prospective study

Abstract

Background: There is limited information on gut microbiota of neonates with congenital gastrointestinal surgical conditions (CGISCs) available.

Methods: This study compared stool microbiota and short-chain fatty acids (SCFAs) of 37 term infants with CGISCs with 36 term healthy infants (HIs). Two stool samples were collected from each infant: as soon as possible after birth (week 1) and 10-14 days of life (week 2).

Results: Bacterial richness and alpha diversity were comparable between CGISCs and HIs at week 1 and week 2 (all p > 0.05). Beta diversity analysis revealed that at week 1, CGISCs had similar community structures to HIs (p = 0.415). However, by week 2, community structures of CGISCs were significantly different from HIs (p = 0.003). At week 1, there were no significant differences in the relative abundances of genera Bifidobacterium and Bacteroides between CGISCs and HIs. At week 2, the relative abundance of Bifidobacterium was significantly lower in CGISCs (mean percentage 7.21 ± 13.49 vs. 28.96 ± 19.6; p = 0.002). Bacteroides were also less abundant in the CGISC group (mean percentage 0.12 ± 0.49 vs. 6.59 ± 8.62; p = 0.039). Relative abundance of genera Pseudomonas and Escherichia-Shigella were higher in CGISCs. At week 2, stool concentrations of all SCFAs were lower in CGISCs (all p < 0.001).

Conclusions: During hospitalization, neonates with CGISCs develop gut dysbiosis and deficiency of SCFAs.

Impact: During hospitalisation, neonates with congenital gastrointestinal surgical conditions develop gut dysbiosis with deficiency of Bifidobacteria and Bacteroides and increased abundance of Escherichia-Shigella and Pseudomonas. They also have low levels of short chain fatty acids in their stools compared to healthy infants. This is the first study evaluating the gut microbiota using 16S ribosomal RNA sequencing methods and stool short chain fatty acids in neonates with congenital gastrointestinal surgical conditions and comparing them to healthy infants. The findings of this study will pave the way for randomised trials of bifidobacterial supplementation in neonates with congenital gastrointestinal surgical conditions.

Fig. 1. Richness and alpha diversity measures of faecal microbiota in the study infants.

The faecal microbiota of CGISC infants demonstrated significant decrease in bacterial richness and alpha diversity shown by Shannon index, ACE and Chao1 from week 1 to week 2 (p < 0.05), while the HI infants exhibited significant decrease in only bacterial richness (p < 0.05) (*p < 0.05; ***p < 0.001).

Fig. 2. Beta diversity measures in the study infants.

Principal coordinate analysis plots of weighted Unifrac distance of the infants at week 1 (a) and week 2 (b). NMDS plots on Bray–Curtis dissimilarity at week 1 (c) and week 2 (d) of the infants. At week 1, HI and CGISC infants had similar community structures (a, c). However, at week 2, HI had significantly different community structure compared to CGISC infants (b, d).

Fig. 3. Relative abundance of the top four phyla in the study infants.

Both CGISC and HI infants have similar levels of the four phyla at week 1. However, at week 2, CGISC infants are significantly enriched for Proteobacteria and lower in abundance for Actinobacteria and Bacteroides.

Fig. 4. Comparison of various genera in study infants.

CGISC infants have signifncantly increased levels of Staphylococcus and Pseudomonas in week 1 compared to HI infants. At week 2, CGISC infants have significantly increased Pseudomonas and Escherichia–Shigella, while HI infants are significantly enriched for Bifidobacterium and Bacteroides.

Fig. 5. Stool SCFA levels in study infants.

At week 1, CGISC infants have significantly lower amounts of total short-chain fatty acid levels and remain so at week 2.