Lipocalin 2 Deficiency Restrains Aging-Related Reshaping of Gut Microbiota Structure and Metabolism

Gut microbiota modulate age-associated changes in metabolism, innate immune responses, and cognitive function. However, the involvement of host factors in the regulation of age-dependent gut microbial structure and intestinal inflammation is largely unknown. Lipocalin 2 (Lcn2) has previously been identified as an adipocytokine and characterized as an important regulator of diet-induced obesity and inflammation. Previous studies have shown that Lcn2 plays a role in high fat diet-induced reshaping of gut microbiota and intestinal inflammation. However, the role of Lcn2 in the regulation of aging-related reshaping of gut microbiota is unclear. Herein, we demonstrate that fecal levels of Lcn2 are reduced during aging. Age reshaped gut microbiota composition in wild-type (WT) mice. Interestingly, Lcn2 deficiency diminished this effect of aging in Lcn2 knockout (LKO) mice, leading to decreased bacterial diversity and increased Firmicutes to Bacteroidetes (F to B) ratio. Specifically, we identified 16 bacteria at the family level that were differentially abundant between WT and LKO mice at old age. Several health-promoting bacteria, including SCFA-producing bacteria, were significantly less prevalent in old LKO mice compared to WT mice, indicating that Lcn2 deficiency shifts the aging-related gut microbial community towards an unhealthy population and lowers microbial butyrate production. Our results provide a line of evidence that Lcn2 plays a role in the control of aging-related reshaping of gut microbiota composition and metabolites.

Download Full-text

Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition

Cells ◽

10.3390/cells8060517 ◽

2019 ◽

Vol 8 (6) ◽

pp. 517 ◽

Cited By ~ 12

Author(s):

Claudia Burrello ◽

Maria Rita Giuffrè ◽

Angeli Dominique Macandog ◽

Angelica Diaz-Basabe ◽

Fulvia Milena Cribiù ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Immune Cells ◽

Intestinal Inflammation ◽

Fecal Microbiota Transplantation ◽

Experimental Colitis ◽

Fecal Microbiota ◽

Microbiota Composition ◽

Chronic Intestinal Inflammation ◽

Gut Microbiota Composition

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

Download Full-text

Microbiome Analysis of Gut Bacterial Communities of Healthy and Diseased Malaysian Mahseer (Tor tambroides)

10.1101/2021.12.08.471852 ◽

2021 ◽

Author(s):

Melinda Mei Lin Lau ◽

Cindy Jia Yung Kho ◽

LEONARD WHYE KIT LIM ◽

Siew Chuiang Sia ◽

Hung Hui Chung ◽

...

Keyword(s):

Gut Microbiota ◽

Bacterial Communities ◽

Alpha Diversity ◽

Microbiota Composition ◽

Petechial Haemorrhage ◽

Rdna Sequencing ◽

Degrading Bacteria ◽

And Function ◽

Gut Microbial Community ◽

Gut Microbiota Composition

Aims: The gut microbiota is referred to an extra organ and is ciritical in assisting the host in terms of nutrition and immunity. Environmental stressors could alter gut microbial community and cause gut inflammation. This study aimed to investigate and compare the gut microbiota community between healthy and diseased Tor tambroides. Methodology and results: In this study, such gut microbial alterations were explored using NGS-based 16S rDNA sequencing on the Malaysian mahseer (T. tambroides). Three adult healthy and three diseased adult Malaysian mahseers (showing signs of exophthalmia, coelomic distension and petechial haemorrhage) were obtained from LTT Aquaculture Sdn Bhd. Our results revealed significant differences in microbial diversity, composition and function between both populations of T. tambroides. Alpha diversity analysis depicts lower diversity of gut microbiota composition in diseased T. tambroides as compared to the healthy group. In particular, Enterobacteriaceae, Aeromonas, Bacteroides, Vibrio and Pseudomonas were found within gut microbiota of the diseased fishes. In addition, cellulose-degrading bacteria and protease-producing bacteria were identified from the gut of T. tambroides. Conclusion, significance and impact of study: Thus, our findings emphasised on the association between the alteration in gut microbiota composition and infectious abdominal dropsy (IAD) in T. tambroides. This finding is important to provide basic information for further diagnosis, prevention and treatment of intestinal diseases in fish.

Download Full-text

Aryl hydrocarbon receptor ligand production by the gut microbiota is decreased in celiac disease leading to intestinal inflammation

Science Translational Medicine ◽

10.1126/scitranslmed.aba0624 ◽

2020 ◽

Vol 12 (566) ◽

pp. eaba0624 ◽

Cited By ~ 3

Author(s):

Bruno Lamas ◽

Leticia Hernandez-Galan ◽

Heather J. Galipeau ◽

Marco Constante ◽

Alexandra Clarizio ◽

...

Keyword(s):

Celiac Disease ◽

Gut Microbiota ◽

Aryl Hydrocarbon Receptor ◽

Intestinal Inflammation ◽

Susceptibility Gene ◽

Rrna Gene ◽

Microbiota Composition ◽

Aryl Hydrocarbon ◽

Pathway Activation ◽

Gut Microbiota Composition

Metabolism of tryptophan by the gut microbiota into derivatives that activate the aryl hydrocarbon receptor (AhR) contributes to intestinal homeostasis. Many chronic inflammatory conditions, including celiac disease involving a loss of tolerance to dietary gluten, are influenced by cues from the gut microbiota. We investigated whether AhR ligand production by the gut microbiota could influence gluten immunopathology in nonobese diabetic (NOD) mice expressing DQ8, a celiac disease susceptibility gene. NOD/DQ8 mice, exposed or not exposed to gluten, were subjected to three interventions directed at enhancing AhR pathway activation. These included a high-tryptophan diet, gavage with Lactobacillus reuteri that produces AhR ligands or treatment with an AhR agonist. We investigated intestinal permeability, gut microbiota composition determined by 16S rRNA gene sequencing, AhR pathway activation in intestinal contents, and small intestinal pathology and inflammatory markers. In NOD/DQ8 mice, a high-tryptophan diet modulated gut microbiota composition and enhanced AhR ligand production. AhR pathway activation by an enriched tryptophan diet, treatment with the AhR ligand producer L. reuteri, or pharmacological stimulation using 6-formylindolo (3,2-b) carbazole (Ficz) decreased immunopathology in NOD/DQ8 mice exposed to gluten. We then determined AhR ligand production by the fecal microbiota and AhR activation in patients with active celiac disease compared to nonceliac control individuals. Patients with active celiac disease demonstrated reduced AhR ligand production and lower intestinal AhR pathway activation. These results highlight gut microbiota-dependent modulation of the AhR pathway in celiac disease and suggest a new therapeutic strategy for treating this disorder.

Download Full-text

Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide

Gut ◽

10.1136/gutjnl-2020-322599 ◽

2021 ◽

pp. gutjnl-2020-322599

Author(s):

Hsin-Chih Lai ◽

Tzu-Lung Lin ◽

Ting-Wen Chen ◽

Yu-Lun Kuo ◽

Chih-Jung Chang ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Inflammation ◽

Chronic Obstructive ◽

Microbiota Composition ◽

Active Components ◽

Toll Like Receptor 4 ◽

Obstructive Pulmonary Disease ◽

Anti Inflammatory ◽

Gut Microbiota Composition

ObjectiveChronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.DesignA murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.ResultsGut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.ConclusionThe gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

Download Full-text

Alleviative Effects of Exopolysaccharide Produced by Lactobacillus helveticus KLDS1.8701 on Dextran Sulfate Sodium-Induced Colitis in Mice

Microorganisms ◽

10.3390/microorganisms9102086 ◽

2021 ◽

Vol 9 (10) ◽

pp. 2086

Author(s):

Yin Liu ◽

Shujuan Zheng ◽

Jiale Cui ◽

Tingting Guo ◽

Jingtao Zhang ◽

...

Keyword(s):

Gut Microbiota ◽

Inflammatory Cytokines ◽

Intestinal Inflammation ◽

Activity Index ◽

Lactobacillus Helveticus ◽

Mucosal Barrier ◽

Microbiota Composition ◽

Mucosal Barrier Function ◽

Anti Inflammatory ◽

Gut Microbiota Composition

Ulcerative colitis (UC) is a non-specific chronic inflammatory disease with lesions located in the colon and rectum. The aim of this study was to evaluate the anti-inflammatory effects of exopolysaccharide-1 (EPS-1) isolated by L. helveticus KLDS1.8701 on UC. The anti-inflammatory effects of EPS-1 were studied using dextran sulphate sodium (DSS)-induced UC model. In vivo results showed that EPS-1 administration significantly ameliorated weight loss, colon shortening, disease activity index (DAI) score, myeloperoxidase (MPO) activity, and colon tissue damage. In addition, EPS-1 administration significantly decreased the levels of pro-inflammatory cytokines and increased levels of anti-inflammatory cytokines. Meanwhile, EPS-1 administration significantly up-regulated the expression of tight junction proteins and mucin. Furthermore, EPS-1 administration modulated gut microbiota composition caused by DSS and increased the short-chain fatty acids (SCFAs) levels. Collectively, our study showed the alleviative effects of EPS- isolated by L. helveticus KLDS1.8701 on DSS-induced UC via alleviating intestinal inflammation, improving mucosal barrier function, and modulating gut microbiota composition.

Download Full-text

Chlorogenic Acid Alleviates Colon Mucosal Damage Induced by a High-Fat Diet via Gut Microflora Adjustment to Increase Short-Chain Fatty Acid Accumulation in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/3456542 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

M. Gui Xie ◽

Y. Quan Fei ◽

Y. Wang ◽

W. Yan Wang ◽

Z. Wang

Keyword(s):

Gut Microbiota ◽

Chlorogenic Acid ◽

Butyric Acid ◽

High Fat Diet ◽

Intestinal Inflammation ◽

Short Chain ◽

Microbiota Composition ◽

High Fat ◽

Anti Inflammatory ◽

Gut Microbiota Composition

A high-fat diet (HFD) has been previously associated with the development of diseases such as chronic colitis. While chlorogenic acid (CGA) is known to exhibit potent antioxidant, antibacterial, and anti-inflammatory properties, little is known about its effects on intestinal inflammation. In this study, we investigated the effects of CGA on intestinal inflammation in an HFD-induced obesity rat model and assessed whether these effects were related to changes in gut microbiota composition. This was achieved by examining physiological and biochemical indicators, the liver transcriptome, and the structure of the fecal microflora. CGA treatment significantly reduced HFD-induced internal organ weight gain, promoted colon tissue repair, downregulated the expression of inflammatory cytokines, and promoted the accumulation of the tight junction protein. KEGG enrichment analysis of differentially expressed genes, applied to data from the RNA-seq of rat liver tissue, revealed that CGA treatment significantly affected amino acid and lipid metabolism in the liver. Furthermore, CGA decreased the abundance of bacteria belonging to the genera Blautia, Sutterella, and Akkermansia and increased butyric acid levels, which were positively correlated with the abundance of Ruminococcus (butyric acid producer). Moreover, the beneficial changes observed in the HFD group were not as pronounced as those in the CGA treatment group. In summary, CGA can alleviate colitis in HFD-induced obesity through its anti-inflammatory effects associated with changes in gut microbiota composition and an increase in the production of short-chain fatty acids and thus can be used as a potential drug for the treatment of this pathology.

Download Full-text