Altered Gut Microbiome Composition and Function Are Associated With Gut Barrier Dysfunction in Healthy Relatives of Patients With Crohn’s Disease

Leibovitzh, Haim; Lee, Sun-Ho; Xue, Mingyue; Garay, Juan A. Raygoza; Hernández-Rocha, Cristian; Madsen, Karen; Meddings, Jonathan B.; Guttman, David S.; Espin‐Garcia, Osvaldo; Smith, Michelle I.; Goethel, Ashleigh; Griffiths, Anne M.; Martin, Paul; Steinhart, A. Hillary; Panancionne, R; Huynh, Hien Q.; Jacobson, K; Aumais, Guy; Mack, David R.; Abreu, María T.; Bernstein, Çharles N.; Marshall, John K.; Turner, Dan; Xu, Wei; Turpin, Williams; Croitoru, Kenneth

doi:10.1053/j.gastro.2022.07.004

Cited by 62 publications

(42 citation statements)

References 53 publications

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“…Numerous studies have demonstrated that gut microbiota play a key role in maintaining the host gut barrier function. , In particular, some studies point to the gut microbiota as a potential target for pesticide-induced host health effects. , Therefore, we further analyzed the effects of AZO on the gut microbiota via 16S rRNA gene sequencing. And, the results found that exposure to L-AZO and H-AZO could significantly altered the microbiota composition in mice.…”

Section: Discussionmentioning

confidence: 99%

Azoxystrobin Disrupts Colonic Barrier Function in Mice via Metabolic Disorders Mediated by Gut Microbiota

Meng

Yan

Sun

et al. 2023

J. Agric. Food Chem.

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The widespread use of azoxystrobin (AZO) over the past few decades has drawn great attention to its environmental health effects. The objective of the present study was to explore the effects of AZO on intestinal barrier function in mice from the perspective of gut microbiota. Specifically, exposure to AZO could cause colonic barrier dysfunction in mice. Meanwhile, AZO could also cause dysbiosis of gut microbiota. Further studies revealed that the metabolic profile of the microbiota was significantly disturbed with AZO exposure. Last but not least, we confirmed that the gut microbiota played a central role in AZO-induced colonic barrier dysfunction through the gut microbiota transplantation experiment. Gut microbiota mediated colonic barrier dysfunction induced by AZO via inducing dysbiosis of the microbiota metabolic profile. The findings of this study strongly support a new insight that the gut microbiota can be a key target of health risks of pesticides.

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Section: Discussionmentioning

confidence: 99%

Azoxystrobin Disrupts Colonic Barrier Function in Mice via Metabolic Disorders Mediated by Gut Microbiota

Meng

Yan

Sun

et al. 2023

J. Agric. Food Chem.

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“…In the present work, we have shown that bacterial composition modifications are an early event in IL-10 deficient mice, starting at week 5 of age—before the development of overt or even subtle colonic inflammation. In this context, Leibovitzh et al (2022) , have recently shown gut microbiota alterations in healthy first-degree relatives of CD patients, associated with intestinal permeability dysfunction. The decrease in the genus Prevotella was observed in the feces and mucosa of IL-10-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice

et al. 2023

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BackgroundDysbiosis and mucin depletion are related with intestinal barrier dysfunction and seems to be an early pathophysiological event in inflammatory bowel disease (IBD). The objective of this work is to study these parameters in the natural history of colitis in IL-10 deficient mice (IL-10−/−).MethodsWild type (WT) and IL-10−/−. mice were followed until sacrifice at 3, 5, 10, 20, 57, and 70 weeks. Body weight, colonic weight/length ratio and in vivo intestinal permeability were registered. Expression of inflammatory and adhesion molecules in the colon was explored by qPCR as Mucin-2 (MUC-2) and molecules involved in goblet cell maturation Interleukin-18 (IL-18) and WAP Four-Disulfide Core Domain 2 (WFDC2), the endoplasmic reticulum stress markers X-box-binding protein (Xbp-1) and Reticulon-4B (RTN-4B). Bacterial composition in feces and colonic mucosa was determined by massive sequencing of the V3–V4 regions of 16S rDNA gene.ResultsIL-10-/- mice showed histological inflammation at weeks 20 and 57, but most notably the intestinal permeability was significantly higher from week 10. Concordantly, the number of goblet cells and expression of MUC-2, IL-18, WFDC2 and Xbp-1 were significantly lower in KO from week 10. Nevertheless, no significant differences were found in the mRNA expression of MUC-2 or Xbp-1 between both groups—derived colon organoids. Significant bacterial differences began at week 5, being the Akkermansia deficiency in KO the most relevant result.ConclusionGut microbiota alterations and mucin depletion are associated with early intestinal barrier dysfunction and precede overt gut inflammation in this animal model of IBD.

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“…However, we did observe that FMT from the donor mice fed the TWD, before DSS-induced colitis, reduced the relative abundance of two bacterial families, Clostridia_UCG-014 and Eubacteriaceae, both in the order Clostridia. In a study involving patients diagnosed with Crohn’s disease and a cohort of healthy first-degree relatives, Leibovitzh et al determined that the abundance of Clostridia_UCG-014 was associated with impaired intestinal permeability, although this association appeared to be independent of gut inflammation [ 44 ]. A recent fecal microbiota analysis of UC patients indicated a reduced abundance of Clostridium cluster IV and Eubacterium rectale compared to healthy controls [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Basal Diet Fed to Recipient Mice Was the Driving Factor for Colitis and Colon Tumorigenesis, despite Fecal Microbiota Transfer from Mice with Severe or Mild Disease

et al. 2023

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Consumption of the total Western diet (TWD) in mice has been shown to increase gut inflammation, promote colon tumorigenesis, and alter fecal microbiome composition when compared to mice fed a healthy diet, i.e., AIN93G (AIN). However, it is unclear whether the gut microbiome contributes directly to colitis-associated CRC in this model. The objective of this study was to determine whether dynamic fecal microbiota transfer (FMT) from donor mice fed either the AIN basal diet or the TWD would alter colitis symptoms or colitis-associated CRC in recipient mice, which were fed either the AIN diet or the TWD, using a 2 × 2 factorial experiment design. Time-matched FMT from the donor mice fed the TWD did not significantly enhance symptoms of colitis, colon epithelial inflammation, mucosal injury, or colon tumor burden in the recipient mice fed the AIN diet. Conversely, FMT from the AIN-fed donors did not impart a protective effect on the recipient mice fed the TWD. Likewise, the composition of fecal microbiomes of the recipient mice was also affected to a much greater extent by the diet they consumed than by the source of FMT. In summary, FMT from the donor mice fed either basal diet with differing colitis or tumor outcomes did not shift colitis symptoms or colon tumorigenesis in the recipient mice, regardless of the basal diet they consumed. These observations suggest that the gut microbiome may not contribute directly to the development of disease in this animal model.

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Altered Gut Microbiome Composition and Function Are Associated With Gut Barrier Dysfunction in Healthy Relatives of Patients With Crohn’s Disease

Cited by 62 publications

References 53 publications

Azoxystrobin Disrupts Colonic Barrier Function in Mice via Metabolic Disorders Mediated by Gut Microbiota

Azoxystrobin Disrupts Colonic Barrier Function in Mice via Metabolic Disorders Mediated by Gut Microbiota

Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice

Basal Diet Fed to Recipient Mice Was the Driving Factor for Colitis and Colon Tumorigenesis, despite Fecal Microbiota Transfer from Mice with Severe or Mild Disease

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