Gut permeability is related to body weight, fatty liver disease, and insulin resistance in obese individuals undergoing weight reduction

Damms-Machado, Antje; Louis, Sandrine; Schnitzer, Anna Ercoli; Volynets, Valentina; Rings, Andreas; Basrai, Maryam; Bischoff, Stephan C.

doi:10.3945/ajcn.116.131110

Cited by 137 publications

(117 citation statements)

References 46 publications

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“…To some extent, these findings indicate that RYGB induced a reduction in inflammation independent of diet control. In this study we did not include a body weight‐matched control group to interpret the extent to which RYGB could reduce intestinal permeability and inflammation; however, in the PF group, partial correction of overweight by dietary limitation was seen to correct the intestinal barrier defect, consistent with previous reports …”

Section: Discussionsupporting

confidence: 84%

“…In this study we did not include a body weight-matched control group to interpret the extent to which RYGB could reduce intestinal permeability and inflammation; however, in the PF group, partial correction of overweight by dietary limitation was seen to correct the intestinal barrier defect, consistent with previous reports. 25,26 Leakage of gut microbiota-derived LPS into the blood induces metabolic endotoxemia, which triggers enhanced inflammation and oxidative stress. 27 Nevertheless, in our previous and other's studies, 4,12 RYGB was shown to induce a markedly higher relative abundance of Proteobacteria, Gammaproteobacteria, and Betaproteobacteria and increased emergence of Fusobacteria and Clostridium, which belong to the Gram-negative bacteria and have been speculated to account for 80% of LPS concentrations in the blood.…”

Section: Discussionmentioning

confidence: 99%

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Roux‐en‐Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats

Guo

Liu

et al. 2019

Journal of Diabetes

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Background Postoperative modulation of the gut microbiome has been suggested to contribute to the metabolic benefits after metabolic surgery, but the mechanisms underlying these metabolic benefits remain unknown. Previously, we reported that Roux‐en‐Y gastric bypass (RYGB) surgery in Zucker diabetic fatty (ZDF) rats increased the abundance of Proteobacteria and Gammaproteobacteria. However, theoretically, these Gram‐negative bacteria may elevate lipopolysaccharide (LPS) levels. Therefore, in this study we further investigated the potential mechanisms by which RYGB improves glucose homeostasis, endotoxemia, and inflammatory stress in ZDF rats. Methods Rats were divided into three groups: (a) an RYGB group (RY); (b) a sham‐operated group pair‐fed with the RY group; and (c) a sham‐operated group fed ad libitum. Changes in LPS, cytokine levels, intestinal permeability (evaluated using the fluorescein isothiocyanate‐dextran method), and intestinal epithelial tight junction proteins zona occludins (ZO)‐1, occludin, and claudin‐1 were assessed 10 weeks postoperatively. Results Rats that underwent RYGB exhibited sustained weight loss and reduced glucose, as well as lower cytokine and LPS concentrations, than rats in the control groups. In the colonic epithelium, ZO1 and claudin‐1 (Cldn1) mRNA levels were higher in the RY than control groups. Intestinal permeability declined in the RY group and was positively correlated with LPS levels and negatively correlated with ZO‐1, occludin, and claudin‐1 expression. Conclusions The results demonstrate that RYGB can reduce the extent of endotoxemia and inflammation, which is associated with improved tight junction integrity and intestinal barrier strength. These effects may explain why a low level of inflammation is maintained after RYGB and the postoperative increase in Gram‐negative bacteria.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Roux‐en‐Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats

Guo

Liu

et al. 2019

Journal of Diabetes

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“…Moreover, there was no significant difference in the value of F/B between T2DM participants and non‐T2DM controls (data not shown). It is well known that the blood microbiome is derived primarily from the gut microbiome as a result of bacterial translocation . However, as previously reported, the blood and gut microbiomes differ significantly from each other, indicating that the intestinal barrier, immune cells, and liver might play a role of filtering and affecting the bacterial translocation .…”

Section: Discussionmentioning

confidence: 62%

Association between blood microbiome and type 2 diabetes mellitus: A nested case‐control study

Qiu

Zhou²,

Yang

et al. 2019

Clinical Laboratory Analysis

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BackgroundAlthough recent studies have indicated that gut microbiome dysbiosis was significantly associated with the onset of type 2 diabetes mellitus (T2DM), information on the role of blood microbiome in T2DM development is scarce.MethodsFifty incident T2DM cases and 100 matched non‐T2DM controls were selected from a prospective cohort study of “135.” The composition of the blood microbiome was characterized using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing from pre‐diagnostic blood sample. The amplicons were normalized, pooled, and sequenced on the Illumina MiSeq instrument using a MiSeq Reagent Kit PE300 v3 kit.ResultsTotally, 3 000 391 and 6 244 227 high‐quality sequences were obtained from T2DM patients and non‐T2DM controls, respectively. The mean diversity of the blood microbiome (Simpson, Chao1 and Shannon indices) was not different between two groups at baseline. At genus level, the Aquabacterium, Xanthomonas, and Pseudonocardia were presented with lower abundance, while Actinotalea, Alishewanella, Sediminibacterium, and Pseudoclavibacter were presented with higher abundance among T2DM cases compared to those in non‐T2DM controls. As the results shown, participants carried the genus Bacteroides in blood were significantly associated with a decreased risk for T2DM development, with 74% vs 88% (adjusted OR: 0.367, 95% CI: 0.151‐0.894). However, participants carried the genus Sediminibacterium have an increased risk for T2DM, with adjusted OR (95% CI) being 14.098 (1.358, 146.330).ConclusionsBlood microbiome may play an etiology role in the development of T2DM. These findings would be useful to develop microbiota‐based strategies for T2DM prevention and control.

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“…The change in apparent oral clearance could be due to downregulation of drug metabolizing enzymes involved in the metabolism of APAP and/or increased bioavailability of APAP. Enzyme regulation and intestinal permeability have been shown to be related to obesity and body weight . However, no difference was seen in the weight‐normalized apparent oral clearance of APAP at 12 months post‐RYGBS compared to baseline.…”

Section: Discussionmentioning

confidence: 94%

The Impact of Proximal Roux‐en‐Y Gastric Bypass Surgery on Acetaminophen Absorption and Metabolism

et al. 2020

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Background Roux‐en‐Y gastric bypass (RYGBS), a surgery that creates a smaller stomach pouch and reduces the length of small intestine, is one of the most common medical interventions for the treatment of obesity. Aim The aim of this study was to determine how RYGBS affects the absorption and metabolism of acetaminophen. Materials and Methods Ten morbidly obese patients received 1.5 g of liquid acetaminophen (APAP) orally on three separate pharmacokinetic study days (i.e., pre‐RYGBS baseline and 3 and 12 months post‐RYGBS). Plasma was collected at pre‐specified timepoints over 24 hours, and the samples were analyzed using liquid chromatography–mass spectrometry for APAP, APAPglucuronide (APAP‐gluc), APAP‐sulfate (APAP‐sulf), APAP‐cysteine (APAP‐cys), and APAP‐Nacetylcysteine (APAP‐nac). Result Following RYGBS, peak APAP concentrations at the 3‐month and 12‐month visits increased by 2.0‐fold compared to baseline (p=0.0039 and p=0.0078, respectively) and the median time to peak concentration decreased from 35 to 10 minutes. In contrast, peak concentrations of APAP‐gluc, APAP‐sulf, APAP‐cys, and APAP‐nac were unchanged following RYGBS. The apparent oral clearance of APAP and the ratios of metabolite area under the curve (AUC)‐to‐APAP AUC for all four metabolites decreased at 3 and 12 months post‐RYGBS compared to the presurgical baseline. In a simulation of expected steady‐state plasma concentrations following multiple dosing of 650 mg APAP every 4 hours, post‐RYGBS patients had higher steady‐state peak APAP concentrations compared to healthy individuals and obese pre‐RYGBS patients, though APAP exposure was unchanged compared to healthy individuals. Conclusion Following RYGBS, the rate and extent of APAP absorption increased and decreased formation of APAP metabolites was observed, possibly due to downregulation of Phase II and cytochrome P450 2E1 enzymes.

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Gut permeability is related to body weight, fatty liver disease, and insulin resistance in obese individuals undergoing weight reduction

Cited by 137 publications

References 46 publications

Roux‐en‐Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats

Roux‐en‐Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats

Association between blood microbiome and type 2 diabetes mellitus: A nested case‐control study

The Impact of Proximal Roux‐en‐Y Gastric Bypass Surgery on Acetaminophen Absorption and Metabolism

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