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Background <p>Although impaired intestinal barrier function is implicated in type 2 diabetes (T2D), its direct in vivo assessment in humans remains challenging, limiting our understanding of the underlying mechanisms. We utilized a novel endoscopic real-time, in situ impedance measurement technique to investigate how hyperglycemia and the intestinal microbiota contribute to intestinal barrier dysfunction in T2D.</p> Methods <p>We validated this impedance-based approach against ex vivo transepithelial electrical resistance (TEER) (<i>r</i> = 0.64,<i> p</i> = 0.011) and applied it to 137 patients undergoing colonoscopy. A mechanistic study (22 T2D, 19 controls) analyzed mucosal microbiota, short-chain fatty acid (SCFA) levels, and tight junction protein gene expression. In vitro assays with Caco-2 monolayers evaluated <i>Bacteroides vulgatus (B. vulgatus)</i> supernatant and high-glucose exposure effects on TEER.</p> Results <p>Patients with T2D had significantly lower ileal impedance (20.9 Ω·cm<sup>2</sup>) compared to controls (24.2 Ω·cm<sup>2</sup>; <i>p</i> &lt; 0.001). Lower <i>Bacteroides</i> abundance correlated with decreased SCFA biosynthesis gene expression and ZO-1 levels. <i>B. vulgatus</i> supernatant counteracted lipopolysaccharide-induced barrier disruption. High-glucose exposure reduced transepithelial electrical resistance (<i>p</i> &lt; 0.05), indicating a direct detrimental effect. Impedance negatively correlated with HbA1c (<i>r</i> = −&#xa0;0.49, <i>p</i> &lt; 0.001), and metformin use was associated with preserved barrier function.</p> Conclusions <p>To our knowledge, this study provides the first direct, in situ evidence that intestinal barrier function is impaired in T2D, a condition associated with concurrent microbial and metabolic alterations. Our findings establish intestinal barrier dysfunction as a key pathophysiological feature of T2D, suggesting that interventions aimed at the intestinal barrier function may represent a novel therapeutic strategy.</p>

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An endoscopic real-time, in situ assessment of intestinal permeability in type 2 diabetes: links to microbiota and hyperglycemia

  • 期刊论文

  • 发表日期：

    2025年11月21日

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  • Yusuke Kimura,
  • Yosuke Minoda,
  • Eikichi Ihara,
  • Haruei Ogino,
  • Kazuki Inamura,
  • Xiaopeng Bai,
  • Yoshimasa Tanaka,
  • Takatoshi Chinen,
  • Ryuichi Sakamoto,
  • Jiro Nakayama,
  • Keita Watanabe,
  • Ikuo Kimura,
  • Yoshihiro Ogawa

摘要

Background

Although impaired intestinal barrier function is implicated in type 2 diabetes (T2D), its direct in vivo assessment in humans remains challenging, limiting our understanding of the underlying mechanisms. We utilized a novel endoscopic real-time, in situ impedance measurement technique to investigate how hyperglycemia and the intestinal microbiota contribute to intestinal barrier dysfunction in T2D.

Methods

We validated this impedance-based approach against ex vivo transepithelial electrical resistance (TEER) (r = 0.64, p = 0.011) and applied it to 137 patients undergoing colonoscopy. A mechanistic study (22 T2D, 19 controls) analyzed mucosal microbiota, short-chain fatty acid (SCFA) levels, and tight junction protein gene expression. In vitro assays with Caco-2 monolayers evaluated Bacteroides vulgatus (B. vulgatus) supernatant and high-glucose exposure effects on TEER.

Results

Patients with T2D had significantly lower ileal impedance (20.9 Ω·cm2) compared to controls (24.2 Ω·cm2; p < 0.001). Lower Bacteroides abundance correlated with decreased SCFA biosynthesis gene expression and ZO-1 levels. B. vulgatus supernatant counteracted lipopolysaccharide-induced barrier disruption. High-glucose exposure reduced transepithelial electrical resistance (p < 0.05), indicating a direct detrimental effect. Impedance negatively correlated with HbA1c (r = − 0.49, p < 0.001), and metformin use was associated with preserved barrier function.

Conclusions

To our knowledge, this study provides the first direct, in situ evidence that intestinal barrier function is impaired in T2D, a condition associated with concurrent microbial and metabolic alterations. Our findings establish intestinal barrier dysfunction as a key pathophysiological feature of T2D, suggesting that interventions aimed at the intestinal barrier function may represent a novel therapeutic strategy.