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. 2022 Feb 17:12:726322.
doi: 10.3389/fcimb.2022.726322. eCollection 2022.

Differences in the Gut Microbiota Composition and Metabolites Associated With Feeding Intolerance in VLBW Infants With a Gestational Age of ≤ 30 Weeks: A Pilot Study

Xiao-Chen Liu  1   2   3   4   5 , Qian Sun  1   2   3   4   5 , Yan-Chun Ji  1   2   3   4   5 , Li-Zhen Fu  1   2   3   4   5 , Zheng-Li Wang  1   2   3   4   5 , Yu He  1   2   3   4   5 , Lu-Quan Li  1   2   3   4   5
Affiliations

Differences in the Gut Microbiota Composition and Metabolites Associated With Feeding Intolerance in VLBW Infants With a Gestational Age of ≤ 30 Weeks: A Pilot Study

Xiao-Chen Liu et al. Front Cell Infect Microbiol. .

Abstract

Objective: To explore the main variations in gut microbiota compositions, short-chain fatty acids (SCFAs) concentrations and autoinducer-2 (AI-2) levels in very-low-birth-weight (VLBW) infants with feeding intolerance (FI).

Methods: Twenty-seven VLBW infants with gestational ages of ≤30 weeks were divided into the FI group (n=14) and feeding tolerance (FT) group (n=13). The gut microbiota composition and SCFAs concentrations and AI-2 levels in feces were detected at 2 and 4 weeks after birth.

Results: There was no difference in alpha diversity between the two groups at 2 and 4 weeks after birth (P>0.05). Although the Chao index decreased (P<0.05), there was no difference in the Shannon index from 2 weeks to 4 weeks in either the FI or FT group (P>0.05). Additionally, there was no difference in beta diversity between the FI and FT groups at 2 weeks (P>0.05), but there was a significant difference in beta diversity between the two groups at 4 weeks (P<0.05) and a large difference from 2 weeks to 4 weeks in both the FI and FT groups (P<0.05). Furthermore, the composition of the microbiota at 4 weeks was significantly different from that at 2 weeks in the FI group (P<0.05). The Veillonella abundance was lower at 4 weeks in the FI group (P<0.05), but there were no differences in the compositions of the other main microbes between the two groups (P>0.05). Proteobacteria and Firmicutes were dominant in both the FI and FT groups. The concentrations of propanoic, valeric and hexanoic acids were lower in the FI group at 2 weeks, and the levels of isobutyric and valeric acids were lower at 4 weeks after birth (P<0.05). The areas under the curves (AUCs) of propanoic, butanoic and valeric acids in predicting FI were 0.878, 0.816 and 0.744, respectively. Compared with that in the FT group, the relative bioluminescence of AI-2 was lower in the FI group at 2 weeks (P<0.05), and the AUC was 0.736.

Conclusions: The main composition of the microbiota was not obviously different in infants with FI. Some SCFAs and AI-2 have moderate value in predicting FI.

Keywords: autoinducer-2 (AI-2); feeding intolerance; gut microbiota; metabolites; short-chain fatty acids (SCFAs).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Alpha diversity of the microbiota in the different groups. There were no differences in the Chao index between the two groups at 2 and 4 weeks after birth, and it decreased from 2 to 4 weeks in both the FT and FI groups (A). There was no difference in the Shannon index between the FI and FT groups or within the FI or FT group at 2 and 4 weeks of life (B). *:P<0.05.
Figure 2
Figure 2
Beta diversity of the microbiota in the different groups. There was no difference in beta diversity between the two groups at 2 weeks (A), but there was a significant difference between the two groups at 4 weeks (P<0.05) (B). The beta diversity of the microbiota at 4 weeks was significantly different from that at 2 weeks in the FT (C) and FI groups (D).
Figure 3
Figure 3
Community abundance in the FI and FT groups. There were no differences between the two groups at the phylum level (A) or genus level (B) at 2 weeks of life. There were no differences between the two groups at the phylum level at 4 weeks after birth (C). The abundance of Veillonella at the genus level was much lower in the FI group than in the FT group at 4 weeks of life (D).
Figure 4
Figure 4
Community abundance within groups. In the FT group, the abundances of Actinobacteria, Bacteroides and Chloroflexi at the phylum level (A) and Clostridium at the genus level (B) were higher at 4 weeks than at 2 weeks of life. The community abundance at the phylum level (C) or at the genus level (D) was not different between 2 and 4 weeks after birth in the FI group.
Figure 5
Figure 5
Comparison of concentrations of SCFAs between the FT and FI groups and between 2 and 4 weeks of life. (A) Total SCFAs, (B) acetic acid, (C) propionic acid, (D) butanoic acid, (E) isobutyric acid, (F) valeric acid, (G) isovaleric acid, (H) hexanoic acid, (I) isohexanoic acid. *P < 0.05.
Figure 6
Figure 6
Identification of the value of some SCFAs in the prediction of FI by ROC analysis. The AUCs of propanoic (A), valeric (B) and hexanoic (C) acids at 2 weeks after birth were 0.878, 0.816 and 0.744, respectively.
Figure 7
Figure 7
Change in AI-2 level in the FT and FI groups and the value of AI-2 in the prediction of FI. The level of AI-2 was lower in the FI group than in the FT group at 2 weeks of life, and there was no difference between the two groups at 4 weeks after birth (A). The AUC for AI-2 at 2 weeks of life was 0.736 (B). *P < 0.05.
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