The Gut–Liver Axis in Chronic Liver Disease: A Macrophage Perspective

Muynck, Kevin De; Vanderborght, Bart; Vlierberghe, Hans Van; Devisscher, Lindsey

doi:10.3390/cells10112959

Cited by 26 publications

(35 citation statements)

References 378 publications

(543 reference statements)

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“…Already 2012 Boonstra et al demonstrated the role of colonic involvement as distinct phenotypical risk factor for PSC also in CD ( 28 ). A causal relationship may exist for translocation of bacterial components through an inflamed and leaky colon into the portal circulation and associated liver inflammation through macrophages and gut-derived T cells ( 29 ). Interestingly, we have not recorded any PSC in L2 CD in our pediatric registry.…”

Section: Discussionmentioning

confidence: 99%

Isolated Crohn's Colitis: Is Localization Crucial? Characteristics of Pediatric Patients From the CEDATA–GPGE Registry

et al. 2022

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IntroductionPediatric patients with inflammatory bowel disease (IBD) are classified into Crohn's disease (CD), ulcerative colitis (UC), and unclassifiable (IBD-U). However, data provide evidence that ileal CD (L1) is distinct from colonic CD (L2). The aim of this study was to investigate the clinical features of isolated Crohn's colitis in a pediatric population.Material and MethodsChildren who were prospectively included in the CEDATA–GPGE registry on diagnosis were compared according to the diagnosis of CD with L2 vs. L1 and ileocolonic (L3) involvement pattern as well as IBD-U and UC. The clinical significance of L2 was investigated with regard to extraintestinal manifestations, treatment, surgery, and disease activity.ResultsFifty-two patients with L2 CD at a median age of 13.4 years (±3.8 SD) were compared with 182 L1 (13.8 ± 2.9 SD), 782 with L3 (12.8 ± 3.3 SD), 653 with UC (12.7 ± 3.8 SD), and 111 patients with IBD-U (11.9 ± 4.7 SD). Bloody stools at diagnosis were more common in L2 (44%) than in L1 (19.7%) and L3 (28.8%), but not as common as in UC (66.5%) and IBD-U (61.3%). Fewer CD patients with L2 (10.2%) received exclusive enteral nutrition therapy (EEN) as induction than patients with L1 (34.3%) and L3 (33.3%). After induction therapy, 42.3% of patients with L2 received immunosuppressants and 21% biologicals during follow-up (L1 56.5/10.5%; L3 59/21%; CU 43.5/11.9%; IBD-U 26.1/12.6%). Extraintestinal manifestations were more frequent in L2 (23.1%) vs. L1 (18.7%), L3 (20.2%), CU (15.8%), and IBD-U (11.7%). The number of patients requiring surgery did not differ within the CD subgroups and was significantly lower in UC and IBD-U. Perianal fistula surgery was significantly more common in L2 (44%) than in L1 (4.8%) or L3 (21.7%). In addition, the frequency of surgery for perianal abscesses was also more frequent in L2 (55.6%) than in L1 (12.7%) or L3 (38.4%).ConclusionsThe consideration of pediatric Crohn's colitis as a distinct disease seems necessary as it is characterized by extraintestinal manifestations (EIMs) with mainly joint involvement and perianal fistulas or abscesses requiring surgery and biologic therapy. Thus, colonic Crohn's disease may have an influence on the therapeutic stratification and should be addressed in further studies.

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Section: Discussionmentioning

confidence: 99%

Isolated Crohn's Colitis: Is Localization Crucial? Characteristics of Pediatric Patients From the CEDATA–GPGE Registry

et al. 2022

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“…К тому же равновесие провоспалительных и противовоспалительных цитокинов может сдвигать течение основного заболевания в сторону прогрессирования или регенерации у пациентов с хроническими прогрессирующими заболеваниями печени [12,33,34,55,[56][57][58][59].…”

Section: бактериальные патоген-ассоциированные паттерны и иммунный ответunclassified

“…Концепция ПИО подразумевает и обратный путь -путь воздействия на микробиом, колонизирующий кишечник. Данная регуляция в полной мере отражает двунаправленность концепции ПИО [12,55,57,62]. Таким образом, печень «очерчивает» микробиоту кишечника посредством высвобождения IgA и желчи.…”

Section: печеночная регуляция микробиоты кишечникаunclassified

“…В свою очередь, желчные кислоты метаболизируются в кишечнике микробиотой, с образованием вторичных желчных кислот, активирующих специфические рецепторы, в частности ядерный рецептор фарнезоида X (FXR) и рецептор желчных кислот, связанных с G-белком -Gpbar1 (также называемых TGR5). Эти рецепторы регулируют многочисленные иммунологические и метаболические пути в организме хозяина, которые могут также косвенно влиять на кишечную микробиоту [8,11,12,57].…”

Section: печеночная регуляция микробиоты кишечникаunclassified

“…Как описывалось выше, микробиота кишечника до некоторой степени модулирует иммунную систему хозяина, а иммунная система оказывает обратное влияние на состав микробиоты кишечника [63,69]. В свою очередь, лимфоидная ткань кишечника, представленная Т-и В-лимфоцитами, антигенпредставляющими клетками и многими другими, играет важную роль в системных и местных иммунных ответах [23,41,57]. Известно также, что микробиота активно формирует системный иммунный ответ хозяина [2, 57,70,71].…”

Section: микробиом и отторжение трансплантатаunclassified

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The «microbiome» of post-liver transplant complications

Salimov

Stoma

Shcherba

et al. 2022

RJTAO

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This paper reviews modern literature and presents a brief analysis of our own data on one of the most pressing issues in modern transplantology and, in particular, transplant hepatology – the role and place of gut-liver axis (GLA) in the early post-transplant period. Objective: to compare the correlation between gut microbiome palette and incidence of certain early postoperative complications in liver transplantation. Materials and methods. The study design is presented as a pilot, prospective, observational, double-blind study based on investigation of the composition of the microbiome residing in the large intestinal in patients that underwent orthotopic liver transplantation (OLTx). The primary cohort of patients consisted of 12 patients who underwent OLTx from a postmortem donor. To assess the gut microbiome palette, biomaterial was collected from all patients in the preand post-transplant period followed by next-generation sequencing. The study was conducted as primary study results registered under number NCT04281797. Results. In the preoperative period, differences close to statistically reliable in relation to Actinobacteria were observed in patients included in the liver transplant waiting list for cirrhosis (LC) and hepatocellular carcinoma (HCC) in cirrhosis. However, due to the pilot nature of the study, this study cohort was limited to an extremely small sample. In turn, in the post-transplant period, there was a statistically significant difference in the taxonomic range of Actinobacteria (p < 0.05) between the above groups, indicating a possible effect of liver transplantation on the gut microbiome. In addition, in the early post-transplant period, there was a marked difference in the microbiome palette between patients with and without acute cellular rejection. Conclusion. GLA and the gut microbiome play a critical role in many liver diseases, and may also have a significant impact on the post-transplant period. In this regard, further research in this direction will not only characterize the predictors and risk factors of bacterial infection and rejection episodes, but will also allow us to form a completely new approach to the treatment tactics for certain complications, including through formation of a microbiota-oriented pharmacotherapy.

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Transient Kupffer cell depletion and subsequent replacement by infiltrating monocyte‐derived cells does not alter the induction or progression of hepatocellular carcinoma

Vanderborght

Muynck

Gijbels

et al. 2023

Intl Journal of Cancer

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Due to a combination of rapid disease progression and the lack of curative treatment options, hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Infiltrated, monocyte‐derived, tumor‐associated macrophages are known to play a role in HCC pathogenesis, but the involvement of Kupffer cells (KCs) remains elusive. Here, we used the Clec4F‐diphteria toxin receptor transgenic mouse model to specifically investigate the effect of KC depletion on HCC initiation, progression and neoplastic growth following liver resection. For this purpose, several HCC mouse models with varying underlying etiologies were used and partial hepatectomy was performed. Our results show that in HCC, developed on a fibrotic or non‐alcoholic steatohepatitis background, depletion of embryonic KCs at the onset of HCC induction and the subsequent replacement by monocyte‐derived KCs does not affect the tumor burden, tumor microenvironment or the phenotype of isolated KCs at end‐stage disease. In non‐chronic liver disease‐associated diethylnitrosamine‐induced HCC, ablation of Clec4F+ KCs did not alter tumor progression or neoplastic growth following liver resection. Our results show that temporal ablation of resident KCs does not impact HCC pathogenesis, neither in the induction phase nor in advanced disease, and indicate that bone marrow‐derived KCs are able to swiftly repopulate the available KC niche and adopt their phenotype.

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The Gut–Liver Axis in Chronic Liver Disease: A Macrophage Perspective

Cited by 26 publications

References 378 publications

Isolated Crohn's Colitis: Is Localization Crucial? Characteristics of Pediatric Patients From the CEDATA–GPGE Registry

Isolated Crohn's Colitis: Is Localization Crucial? Characteristics of Pediatric Patients From the CEDATA–GPGE Registry

The «microbiome» of post-liver transplant complications

Transient Kupffer cell depletion and subsequent replacement by infiltrating monocyte‐derived cells does not alter the induction or progression of hepatocellular carcinoma

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