Exclusive Enteral Nutrition Alleviates Th17-Mediated Inflammation via Eliminating Mechanical Stress–Induced Th17-Polarizing Cytokines in Crohn’s-like Colitis

Geesala, Ramasatyaveni; Zhang, Ke; Lin, You-Min; Johnson, John C.; Cong, Yingzi; Cohn, Steven M.; Shi, Xuan-Zheng P.

doi:10.1093/ibd/izad158

Cited by 3 publications

(8 citation statements)

References 36 publications

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“…Crohn's-like colitis was induced by an intracolonic instillation of TNBS 65 mg/kg in 250 µL of 40% ethanol [12,19]. As reported previously [12,15], this treatment induces transmural and stenotic inflammation mimicking Crohn's disease in the colon. Sham control rats were treated with an intracolonic instillation of 250 µL of saline.…”

Section: Introductionmentioning

confidence: 76%

“…Other reports demonstrated an improved epithelial permeability [14]. Our recent studies have revealed that EEN may exert its beneficial effects by eliminating mechanical stress and attenuating mechanical stress-induced pro-inflammatory mediators in CD [15]. However, the effect of EEN on the gut microbiome has not been well addressed in these reports.…”

Section: Introductionmentioning

confidence: 90%

“…Sham control rats were treated with saline instillation. The instillation procedure was performed by utilizing a catheter inserted 7 cm inside of the anus, as previously described [12,15]. Before the TNBS or saline instillation, rats were fasted and treated with bowel cleanser for 24 h. The saline-or TNBS-treated rats were fed ad libitum either with regular pellet food (Picolab Rodent Diet 5053) or EEN liquid diet (Ensure Clear; Abbott, Abbott Park, IL, USA) for 7 days.…”

Section: Induction Of Crohn's-like Colitis and Een Treatmentmentioning

confidence: 99%

“…Fecal pellets were collected from the distal colon for microbiome analysis [20]. Body weight changes, inflammation score, and the disease activity index (DAI) (on a 6.0 scale) were determined as described earlier [15].…”

Section: Induction Of Crohn's-like Colitis and Een Treatmentmentioning

confidence: 99%

“…Total RNA was isolated from the colonic tissues from all the four groups of rats using RNeasy Mini Kit according to the manufacturer's protocol (Qiagen, Valencia, CA, USA) [21], and reverse transcribed to cDNA with Bio-Rad iScript reverse transcriptase (Bio-Rad). Real-time quantitative RT-PCR was performed using the Bio-Rad CFX9000 Thermocycler (Hercules, CA, USA), as described previously [15,21]. TaqMan probes for interleukin-17 (IL-17) (Rn01757168_m1) and interferon-gamma (IFN-γ) (Rn01649192_m1) were purchased from Thermo Fisher Scientific (Waltham, MA, USA).…”

Section: Colonic Tissue Preparations and Quantitative Real-time Polym...mentioning

confidence: 99%

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Exclusive Enteral Nutrition Beneficially Modulates Gut Microbiome in a Preclinical Model of Crohn’s-like Colitis

Geesala,

Recharla,

Zhang

et al. 2024

Nutrients

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Exclusive enteral nutrition (EEN) is an established dietary treatment for Crohn’s disease (CD) by alleviating inflammation and inducing remission. However, the mechanisms of action of EEN are incompletely understood. As CD is associated with gut microbiome dysbiosis, we investigated the effect of EEN on the microbiome in a rat model of CD-like colitis. The rat model of CD-like colitis was established by an intracolonic instillation of TNBS at 65 mg/kg in 250 µL of 40% ethanol. Sham control rats were instilled with saline. Rats were fed ad libitum with either regular pellet food or EEN treatment with a clear liquid diet (Ensure). Rats were euthanized at 7 days. Fecal pellets were collected from the distal colon for 16S rRNA sequencing analysis of gut microbiota. In addition, colon tissues were taken for histological and molecular analyses in all the groups of rats. EEN administration to TNBS-induced CD rats significantly improved the body weight change, inflammation scores, and disease activity index. The mRNA expression of IL-17A and interferon-γ was significantly increased in the colonic tissue in TNBS rats when fed with regular food. However, EEN treatment significantly attenuated the increase in IL-17A and interferon-γ in TNBS rats. Our 16S rRNA sequencing analysis found that gut microbiota diversity and compositions were significantly altered in TNBS rats, compared to controls. However, EEN treatment improved alpha diversity and increased certain beneficial bacteria such as Lactobacillus and Dubosiella and decreased bacteria such as Bacteroides and Enterorhabdus in CD-like rats, compared to CD-like rats with the regular pellet diet. In conclusion, EEN treatment increases the diversity of gut microbiota and the composition of certain beneficial bacteria. These effects may contribute to the reduced inflammation by EEN in the rat model of CD-like colitis.

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Section: Introductionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 90%

Section: Induction Of Crohn's-like Colitis and Een Treatmentmentioning

confidence: 99%

Section: Induction Of Crohn's-like Colitis and Een Treatmentmentioning

confidence: 99%

Section: Colonic Tissue Preparations and Quantitative Real-time Polym...mentioning

confidence: 99%

See 3 more Smart Citations

Exclusive Enteral Nutrition Beneficially Modulates Gut Microbiome in a Preclinical Model of Crohn’s-like Colitis

Geesala,

Recharla,

Zhang

et al. 2024

Nutrients

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Inflammation-related Proteins Support Diagnosis of Inflammatory Bowel Disease and Are Modified by Exclusive Enteral Nutrition in Children With Crohn’s Disease, Especially of Ileal Phenotype

White,

Svolos,

Gervais

et al. 2024

Inflammatory Bowel Diseases

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Background The immunological effects of treatment with exclusive enteral nutrition (EEN) in Crohn’s disease (CD) remain unknown. We characterized the plasma levels of inflammation-related proteins (IRPs) in children with CD and ulcerative colitis (UC) compared with noninflammatory controls (non-IBD) and explored the effect of EEN in CD. Methods Ninety-two IRPs were quantified using Olink proteomics in children with CD (n = 53), UC (n = 11), and non-IBD (n = 19). For 18 children with active CD, IRPs were measured before and after 8 weeks of EEN. Relationships with disease phenotype and response to EEN were studied. Results Compared with non-IBD, patients with active UC and CD had different levels of 27 (24 raised, 3 decreased) and 29 (26 raised, 3 decreased) IRPs, respectively. Exclusive enteral nutrition modified the levels of 19 IRPs (13 increased, 6 decreased including CCL23, interleukin-24, interleukin-6, and MMP-1). More pronounced changes in IRP profile were observed in patients with ileal involvement and a ≥50% decrease in fecal calprotectin during EEN compared with those with colonic involvement and a <50% decrease in fecal calprotectin, respectively. A machine-learning model utilizing baseline IRP profile predicted response to EEN with a sensitivity of 89%, specificity of 57%, and accuracy of 73%. Thymic stromal lymphopoietin was the most important IRP in the model, this being higher in responders. Conclusions Inflammation-related proteins may be useful in the differential diagnosis of IBD. Exclusive enteral nutrition extensively modulated IRPs levels in children with active CD with more pronounced effects observed in patients who showed a reduction in FC and had ileal disease involvement.

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Mechanical stress-induced connective tissue growth factor plays a critical role in intestinal fibrosis in Crohn’s-like colitis

Lin,

Zhang,

Geesala

et al. 2024

American Journal of Physiology-Gastrointestinal and Liver Physi

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Crohn's disease (CD) is an inflammatory bowel disease characterized by transmural inflammation and intestinal fibrosis. Mechanisms of fibrosis in CD are not well understood. Transmural inflammation is associated with inflammatory cell infiltration, stenosis, and distention, which present mechanical stress (MS) to the bowel wall. We hypothesize that MS induces gene expression of pro-fibrotic mediators such as connective tissue growth factor (CTGF), which may contribute to fibrosis in CD. A rodent model of CD was induced by intracolonic instillation of TNBS to the distal colon. TNBS instillation induced a localized transmural inflammation (site I), with a distended colon segment (site P) proximal to site I. We detected significant fibrosis and collagen content not only in site I, but also in site P in CD rats by day 7. CTGF expression increased significantly in sites P and I, but not in the segment distal to the inflammation site. Increased CTGF expression was detected mainly in the smooth muscle cells (SMC). When rats were fed exclusively with clear liquid diet to prevent mechanical distention in colitis, expression of CTGF in sites P and I was blocked. Direct stretch led to robust expression of CTGF in colonic SMC. Treatment of CD rats with anti-CTGF antibody FG-3149 reduced fibrosis and collagen content in both sites P and I and exhibited consistent trends towards normalizing expression of collagen mRNAs. In conclusion, our studies suggest that mechanical stress, by up-regulating pro-fibrotic mediators i.e. CTGF, may play a critical role in fibrosis in CD.

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Exclusive Enteral Nutrition Alleviates Th17-Mediated Inflammation via Eliminating Mechanical Stress–Induced Th17-Polarizing Cytokines in Crohn’s-like Colitis

Cited by 3 publications

References 36 publications

Exclusive Enteral Nutrition Beneficially Modulates Gut Microbiome in a Preclinical Model of Crohn’s-like Colitis

Exclusive Enteral Nutrition Beneficially Modulates Gut Microbiome in a Preclinical Model of Crohn’s-like Colitis

Inflammation-related Proteins Support Diagnosis of Inflammatory Bowel Disease and Are Modified by Exclusive Enteral Nutrition in Children With Crohn’s Disease, Especially of Ileal Phenotype

Mechanical stress-induced connective tissue growth factor plays a critical role in intestinal fibrosis in Crohn’s-like colitis

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