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Background <p>Intestinal microbiota has a role in early life maturation including maturation of intestinal immune function. However, the interaction of the TLR4 with colonizing bacteria in intestinal development is incompletely understood.</p> Methods <p>An established human immature small intestinal cell line, human fetal intestinal organoids, and wild-type (WT) and TLR4 gene knockout (TLR4 <sup>−/−</sup>) neonatal mice were used to test the synergism between the innate immune receptor TLR4 and postbiotics from <i>Bifidobacteria longum</i> subsp. <i>infantis</i> (<i>B. infantis</i>) in development of the premature intestine.</p> Results <p>TLR4-mediated postbiotics induced immature enterocyte proliferation and filamentous actin (F-actin) maturation both at the mRNA and protein levels. Proliferation of mRNA levels increased in wild-type mice but not in TLR4 <sup>−/−</sup> mice fed by postbiotics, both in the ileum and colon. Postbiotics can also change tight junction distribution in WT neonatal colon but not in TLR4 <sup>−/−</sup> mice.</p> Conclusions <p>Our data suggest a novel regulation of intestinal development by a synergistic role of the innate immune receptor TLR4 and early life colonizing bacteria, such as <i>B. infantis</i>. This study should provide new insights into the mechanisms of intestinal maturation as well as opportunities to target novel approaches to NEC prevention and treatment.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>The innate immune system and postbiotics affect immature intestinal development.</p> </ItemContent> <ItemContent> <p>The innate immune receptor TLR4 prevention of NEC.</p> </ItemContent> <ItemContent> <p>Mechanism of prevention of NEC.</p> </ItemContent> <ItemContent> <p>This is the first time this has been demonstrated in human fetal intestine.</p> </ItemContent> <ItemContent> <p>In vitro process for future clinical studies for prevention of NEC.</p> </ItemContent> </UnorderedList></p>

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Synergism between TLR4 and B. infantis in the development of the premature intestine

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月12日

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  • Wuyang Huang,
  • Karim Djebali,
  • Ky Young Cho,
  • Kimberly Gardner,
  • Alessio Fasano,
  • Di Meng,
  • W. Allan Walker

摘要

Background

Intestinal microbiota has a role in early life maturation including maturation of intestinal immune function. However, the interaction of the TLR4 with colonizing bacteria in intestinal development is incompletely understood.

Methods

An established human immature small intestinal cell line, human fetal intestinal organoids, and wild-type (WT) and TLR4 gene knockout (TLR4 −/−) neonatal mice were used to test the synergism between the innate immune receptor TLR4 and postbiotics from Bifidobacteria longum subsp. infantis (B. infantis) in development of the premature intestine.

Results

TLR4-mediated postbiotics induced immature enterocyte proliferation and filamentous actin (F-actin) maturation both at the mRNA and protein levels. Proliferation of mRNA levels increased in wild-type mice but not in TLR4 −/− mice fed by postbiotics, both in the ileum and colon. Postbiotics can also change tight junction distribution in WT neonatal colon but not in TLR4 −/− mice.

Conclusions

Our data suggest a novel regulation of intestinal development by a synergistic role of the innate immune receptor TLR4 and early life colonizing bacteria, such as B. infantis. This study should provide new insights into the mechanisms of intestinal maturation as well as opportunities to target novel approaches to NEC prevention and treatment.

Impact

The innate immune system and postbiotics affect immature intestinal development.

The innate immune receptor TLR4 prevention of NEC.

Mechanism of prevention of NEC.

This is the first time this has been demonstrated in human fetal intestine.

In vitro process for future clinical studies for prevention of NEC.