Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations

Moschen, Alexander R.; Gerner, Romana R.; Wang, Jun; Klepsch, Victoria; Adolph, Timon E.; Reider, Simon; Hackl, Hubert; Pfister, A; Schilling, Johannes; Moser, Patrizia; Kempster, Sarah; Swidsinski, Alexander; Orth‐Höller, Dorothea; Weiss, Günter; Baines, John F.; Kaser, Arthur; Tilg, Herbert

doi:10.1016/j.chom.2016.03.007

Cited by 281 publications

(224 citation statements)

References 38 publications

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“…Cohousing Lcn2 -/- and Il-10 -/- mice exacerbated colitis in the latter (8). Consistently, Moschen et al reported that Lcn2 -/- / Il-10 -/- mice developed spontaneous colitis and invasive right-sided tumors due to dysregulated microbiota (9**). In particular, LCN2 inhibits growth of Alistipes spp.…”

Section: Barrier Functionmentioning

confidence: 72%

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Novel insights into microbiome in colitis and colorectal cancer

Yang¹,

Jobin

2017

Current Opinion in Gastroenterology

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Purpose of review Microbiota is a major component of the etiology of inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Here, we summarize key advances achieved the past 18 months (ending June 2017) toward a better understanding of the role of microbiota in colitis and CRC development. Recent findings Accumulating evidence shows the essential role of intestinal barrier function (e.g., mucus, IgA, LCN2, LYPD8) in protecting against bacteria-induced inflammation and tumor development. Numerous signaling pathways (e.g., TLRs, NLRs), metabolites (e.g., indole, bile acids, retinoic acid) and small non-coding RNAs (e.g., miRNA) have been identified as key mediators regulating host-microbe interactions in the intestine. Novel microbial drivers of colitis and tumorigenesis (e.g., Alistipes finegoldii, Atopobium parvalum, Peptostreptococcus anaerobius) have been identified and their disease-promoting activities have been described. Summary IBD-associated colorectal cancer results from a complex breakdown of communication between the host and its microbiota, involving barrier function, immune signaling and metabolites.

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Section: Barrier Functionmentioning

confidence: 72%

“…In particular, LCN2 inhibits growth of Alistipes spp. (9**), which are associated with human CRC (10). Alistipes finegoldii colonization induces CAC development via activation of IL-6/STAT3 signaling in Il-10 -/- mice (9**).…”

Section: Barrier Functionmentioning

confidence: 99%

Novel insights into microbiome in colitis and colorectal cancer

Yang¹,

Jobin

2017

Current Opinion in Gastroenterology

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“…83 However, causality to FMT remains unclear. The transmission of malignant, autoimmune, metabolic or neuropsychiatric diseases have been discussed and at least partially shown in animal models 84. Patients with CDI are known to be at high risk of postinfectious IBS 85.…”

Section: Resultsmentioning

confidence: 99%

“…The transmission of malignant, autoimmune, metabolic or neuropsychiatric diseases have been discussed and at least partially shown in animal models. 84 Patients with CDI are known to be at high risk of postinfectious IBS. 85 However, the role of FMT in this context has to be elucidated.…”

Section: Short-term Monitoring Of Patients For Adverse Eventsmentioning

confidence: 99%

European consensus conference on faecal microbiota transplantation in clinical practice

Cammarota

Ianiro

Tilg

et al. 2017

Gut

Self Cite

906

848

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Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.

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“…We observed that Ruminococcus torques , involved in mucus degradation and gut barrier dysfunction [58], positively correlated with the increase in SBP. Furthermore, both Eubacterium siraeum and A. finegoldii , known to trigger intestinal inflammation [59,60], positively correlated with SBP. Although further validation is needed, this suggests that certain gut bacteria may drive intestinal gut barrier dysfunction and inflammation, which was confirmed by measurement of plasma markers and gut-targetted proinflammatory cells (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

et al. 2018

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Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut–epithelial barrier function markers and microbiome composition could predict systolic BP (SBP). Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability. Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP. Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001). Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001). The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP. These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans. They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.

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Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations

Cited by 281 publications

References 38 publications

Novel insights into microbiome in colitis and colorectal cancer

Novel insights into microbiome in colitis and colorectal cancer

European consensus conference on faecal microbiota transplantation in clinical practice

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

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