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Specific microbiome changes in a mouse model of parenteral nutrition associated liver injury and intestinal
J Kirk Harris1, Karim C El Kasmi2, Aimee L Anderson2
1Department of Pediatrics, Section of Pulmonary Medicine, University of Colorado, Aurora, Colorado, United States of America.
Insights
Parenteral nutrition-associated liver injury (PNALI) in infants is linked to specific gut bacteria, particularly Erysipelotrichaceae, and soy-derived plant sterols. Modifying PN lipid composition may help manage PNALI by altering these bacterial communities.
Area of Science:
- Gastroenterology
- Microbiology
- Pediatric Hepatology
Background:
- Parenteral nutrition (PN) is crucial for infants unable to tolerate enteral feeding but can cause PN-associated liver injury (PNALI).
- Previous research established a mouse model for PNALI involving PN infusion and intestinal injury, highlighting roles for TLR4 signaling, soy sterols, and Kupffer cells (KCs).
Purpose of the Study:
- To investigate the alterations in the intestinal microbiome associated with PNALI in a mouse model.
- To explore the relationship between gut microbiota composition, PN lipid content, and PNALI development.
Main Methods:
- Microbiome analysis of colonic microbiota in PNALI and control mice.
- Assessment of PNALI severity following interventions such as enteral antibiotic treatment, PN lipid emulsion modification, and addition of soy-derived plant sterols.
Main Results:
- PNALI mice exhibited significant alterations in colonic microbiota, notably an increase in Erysipelotrichaceae and specific Bacteroidetes lineages (S24-7).
- Enteral antibiotic treatment and removal of soy oil-based lipid emulsions from PN attenuated PNALI and reduced Erysipelotrichaceae abundance.
- Addition of soy-derived plant sterols (stigmasterol) to fish oil-based PN restored Erysipelotrichaceae and PNALI.
Conclusions:
- Soy-derived plant sterols in PN are associated with specific colonic bacterial groups, including Erysipelotrichaceae, which contribute to PNALI.
- Bacterial products may activate KCs, promoting PNALI.
- Modifying PN lipid composition offers a potential strategy for managing PNALI by targeting associated intestinal bacteria.
Background:
Parenteral nutrition (PN) has been a life-saving treatment in infants intolerant of enteral feedings. However, PN is associated with liver injury (PN Associated Liver Injury: PNALI) in a significant number of PN-dependent infants. We have previously reported a novel PNALI mouse model in which PN infusion combined with intestinal injury results in liver injury. In this model, lipopolysaccharide activation of toll-like receptor 4 signaling, soy oil-derived plant sterols, and pro-inflammatory activation of Kupffer cells (KCs) played key roles. The objective of this study was to explore changes in the intestinal microbiome associated with PNALI.
Methodology And Principal Findings:
Microbiome analysis in the PNALI mouse identified specific alterations within colonic microbiota associated with PNALI and further association of these communities with the lipid composition of the PN solution. Intestinal inflammation or soy oil-based PN infusion alone (in the absence of enteral feeds) caused shifts within the gut microbiota. However, the combination resulted in accumulation of a specific taxon, Erysipelotrichaceae (23.8% vs. 1.7% in saline infused controls), in PNALI mice. Moreover, PNALI was markedly attenuated by enteral antibiotic treatment, which also was associated with significant reduction of Erysipelotrichaceae (0.6%) and a Gram-negative constituent, the S24-7 lineage of Bacteroidetes (53.5% in PNALI vs. 0.8%). Importantly, removal of soy oil based-lipid emulsion from the PN solution resulted in significant reduction of Erysipelotrichaceae as well as attenuation of PNALI. Finally, addition of soy-derived plant sterol (stigmasterol) to fish oil-based PN restored Erysipelotrichaceae abundance and PNALI.
Conclusions:
Soy oil-derived plant sterols and the associated specific bacterial groups in the colonic microbiota are associated with PNALI. Products from these bacteria may directly trigger activation of KCs and promote PNALI. Furthermore, the results indicate that lipid modification of PN solutions may alter specific intestinal bacterial species associated with PNALI, and thus suggest strategies for management of PNALI.
