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Impact of hepatocyte growth factor on the colonic morphology and gut microbiome in short bowel syndrome rat model

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Abstract

Purpose

This study aimed to investigate the impact of hepatocyte growth factor (HGF) on colonic morphology and gut microbiota in a rat model of short bowel syndrome (SBS).

Methods

SD rats underwent jugular vein catheterization for total parenteral nutrition (TPN) and 90% small bowel resection [TPN + SBS (control group) or TPN + SBS + intravenous HGF (0.3 mg/kg/day, HGF group)]. Rats were harvested on day 7. Colonic morphology, gut microflora, tight junction, and Toll-like receptor-4 (TLR4) were evaluated.

Results

No significant differences were observed in the colonic morphological assessment. No significant differences were observed in the expression of tight junction-related genes in the proximal colon. However, the claudin-1 expression tended to increase and the claudin-3 expression tended to decrease in the distal colon of the HGF group. The Verrucomicrobiota in the gut microflora of the colon tended to increase in the HGF group. The abundance of most LPS-producing microbiota was lower in the HGF group than in the control group. The gene expression of TLR4 was significantly downregulated in the distal colon of the HGF group.

Conclusion

HGF may enhance the mucus barrier through the tight junctions or gut microbiome in the distal colon.

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Fig. 1
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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

SBS:

Short bowel syndrome

TPN:

Total parenteral nutrition

IFALD:

Intestinal failure-associated liver disease

HGF:

Hepatocyte growth factor

MSBR:

Massive small bowel resection

PCR:

Real-time polymerase chain reaction

ZO-1:

Zonula occludens-1

TLR4:

Toll-like receptor-4

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Acknowledgements

This study was supported by the Laboratory Animal Science Research Support Center Institute for Research Promotion, Kagoshima University. The authors thank Mr. Brian Quinn for his comments and assistance in this manuscript. The authors thank Tomomi Kamibayashiyama, a technician at our institution, for her help with the management of the rat, histopathological measurements, and RT-PCR analyses. The authors thank Orie Iwaya, a technician at the Department of Pathology, Graduate School of Medical and Dental Science, for her help with the histopathological staining. This study was supported by the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS: 23K08031, 22K07848, 22K07894, 22K08719, 22K08736, 22K08757, 21K07867, and 21K08623) and a Grant from the Kawano Masanori Memorial Foundation for Promotion of Pediatrics.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan

    Koshiro Sugita, Keisuke Yano, Shun Onishi, Yumiko Tabata, Yumiko Iwamoto, Masato Ogata, Lynne Takada, Chihiro Kedoin, Masakazu Murakami, Toshio Harumatsu, Takafumi Kawano, Mitsuru Muto & Satoshi Ieiri

  2. Department of Pediatric Surgery, Kagoshima City Hospital, Kagoshima, Japan

    Makoto Matsukubo

  3. Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, School of Medical and Dental Sciences, Kagoshima University Graduate, Kagoshima, Japan

    Kotaro Kumagai & Akio Ido

  4. Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan

    Tatsuru Kaji

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  1. Koshiro Sugita
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Contributions

K.S., K.Y., and M.M. designed the study. K.S., K.Y., S.O., and T.K. performed experiments. Y.I., M.O., and L.T. supported the histopathological assessment. Y.T., K.C., M.M., T.H., and K.S. analyzed the data and created the Tables and Figures. M.M., K.K., A.I., and T.K. provided conceptual advice. K.S. wrote the manuscript in consultation with S.I.

Corresponding author

Correspondence to Satoshi Ieiri.

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Koshiro Sugita and other co-authors declare no conflicts of interest.

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Sugita, K., Yano, K., Onishi, S. et al. Impact of hepatocyte growth factor on the colonic morphology and gut microbiome in short bowel syndrome rat model. Pediatr Surg Int 40, 185 (2024). https://doi.org/10.1007/s00383-024-05776-z

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