scholarly journals Impairment of Intestinal Barrier Function Induced by Early Weaning via Autophagy and Apoptosis Associated With Gut Microbiome and Metabolites

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjie Tang ◽  
Jingliang Liu ◽  
Yanfei Ma ◽  
Yusen Wei ◽  
Jianxin Liu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Clustering Coefficient ◽  
Autophagic Flux ◽  
Early Weaning ◽  
Microbial Composition ◽  
Apoptosis Pathway

Early weaning piglet is frequently accompanied by severe enteric inflammatory responses and microbiota dysbiosis. The links between the gut microbiome and the etiology of gut inflammation are not fully understood. The study is aimed to investigate the potential molecular mechanisms mediating inflammatory reactivity following early weaning, and to find whether these changes are correlated with gut microbiota and metabolite signatures by comparison between suckling piglets (SPs) and weaning piglets (WPs). Histopathology analysis showed a severe inflammatory response and the disruption of epithelial barrier function. Early weaning resulted in reduced autophagy indicated as the suppression of autophagic flux, whereas induced the TLR4/P38MAPK/IL-1β-mediated apoptotic pathway, as well as activation of the IL-1β precursor. The alpha-diversity and microbial composition were changed in WPs, such as the decreased abundances of Bifidobacterium, Bacteroides, Bacillus, Lactobacillus, and Ruminococcus. Microbial co-concurrence analysis revealed that early weaning significantly decreased network complexity, including network size, degree, average clustering coefficient and number of keystone species, as compared with the SP group. Differentially abundant metabolites were mainly associated with amino acid and purine metabolism. Strong correlations were detected between discrepant microbial taxa and multiple inflammatory parameters. In conclusion, we found that dysregulations of autophagy and apoptosis pathway were involved in colon inflammation during weaned period, which may result from gut microbiota dysbiosis. This study may provide possible intervention modalities for preventing or treating post-weaning infections through maintaining gut microbial ecosystem integrity.

scholarly journals Aberrant Gut Microbiome Contributes to Intestinal Oxidative Stress, Barrier Dysfunction, Inflammation and Systemic Autoimmune Responses in MRL/lpr Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Wang ◽  
Gangduo Wang ◽  
Nivedita Banerjee ◽  
Yuejin Liang ◽  
Xiaotang Du ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gut Microbiome ◽  
Barrier Function ◽  
Inflammatory Responses ◽  
Barrier Dysfunction ◽  
Microbial Composition ◽  
Fecal Microbiome ◽  
Permeability Changes ◽  
Systemic Autoimmunity ◽  
Junction Protein

Microbiome composition and function have been implicated as contributing factors in the pathogenesis of autoimmune diseases (ADs), including systemic lupus erythematosus (SLE), rheumatoid arthritis and autoimmune hepatitis (AIH). Furthermore, dysbiosis of gut microbiome is associated with impaired barrier function and mucosal immune dysregulation. However, mechanisms by which gut microbiome contributes to the ADs and whether antioxidant treatment can restore gut homeostasis and ameliorate the disease outcome are not known. This study was, therefore, focused on examining the involvement of gut microbiome and host responses in the pathogenesis of SLE using unique female mouse models (C57BL/6, MRL+/+ and MRL/lpr) of 6 and 18 weeks with varying degrees of disease progression. Fecal microbiome diversity and composition, gut oxidative stress (OS), barrier function and inflammation, as well as systemic autoimmunity were determined. Interestingly, each mouse strain had distinct bacterial community as revealed by β-diversity. A lower Firmicutes/Bacteroidetes ratio in 6-week-old MRL/lpr mice was observed, evidenced by decrease in Peptostreptococcaceae under Firmicutes phylum along with enrichment of Rikenellaceae under Bacteroidetes phylum. Additionally, we observed increases in colonic OS [4-hydroxynonenal (HNE)-adducts and HNE-specific immune complexes], permeability changes (lower tight junction protein ZO-2; increased fecal albumin and IgA levels) and inflammatory responses (increased phos-NF-κB, IL-6 and IgG levels) in 18-week-old MRL/lpr mice. These changes were associated with markedly elevated AD markers (antinuclear and anti-smooth muscle antibodies) along with hepatic portal inflammation and severe glomerulonephritis. Notably, antioxidant N-acetylcysteine treatment influenced the microbial composition (decreased Rikenellaceae; increased Akkeransiaceae, Erysipelotrichaceae and Muribaculaceae) and attenuated the systemic autoimmunity in MRL/lpr mice. Our data thus show that gut microbiome dysbiosis is associated with increased colonic OS, barrier dysfunction, inflammatory responses and systemic autoimmunity markers. These findings apart from delineating a role for gut microbiome dysbiosis, also support the contribution of gut OS, permeability changes and inflammatory responses in the pathogenesis of ADs.

scholarly journals Postoperative Complications Are Associated with Long-Term Changes in the Gut Microbiota Following Colorectal Cancer Surgery

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 246
Author(s):  
Felix C.F. Schmitt ◽  
Martin Schneider ◽  
William Mathejczyk ◽  
Markus A. Weigand ◽  
Jane C. Figueiredo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Postoperative Complications ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Tumor Resection ◽  
Microbial Composition ◽  
Colorectal Cancer Surgery ◽  
Long Term Changes ◽  
Stool Samples

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.

scholarly journals Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients

2021 ◽  
Author(s):  
Yueqiong Ni ◽  
Zoltan Lohinai ◽  
Yoshitaro Heshiki ◽  
Balazs Dome ◽  
Judit Moldvay ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Cancer Patients ◽  
Gut Microbiome ◽  
Human Gut ◽  
Microbial Composition ◽  
Shotgun Metagenomics ◽  
Lung Cancer Patients ◽  
Microbial Species ◽  
Functional Pathways

AbstractCachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.

scholarly journals Impact of the gut microbiome on the atorvastatin-dependent modulation of the serum lipidome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Roessler ◽  
F Zimmermann ◽  
D Schmidt ◽  
U Escher ◽  
A Jasina ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Interindividual Variation ◽  
Funding Source ◽  
Microbial Composition ◽  
Atorvastatin Treatment ◽  
Qrt Pcr ◽  
16S Rna ◽  
Regulatory Properties

Abstract Background and aims The modulation of serum lipids, in particular of the low-density lipoprotein cholesterol (LDL-C), by statins varies between individuals. The mechanisms regulating this interindividual variation are only poorly understood. Here, we investigated the relation between the gut microbiome and the regulatory properties of atorvastatin on the serum lipidome using mice with depleted gut microbiome. Methods Over a period of 6 weeks, mice (C57BL/6) with either an intact (conventional mice, CONV, n=24) or antibiotic-based depleted gut microbiome (antibiotic treated mice, ABS, n=16) were put on standard chow diet (SCD) or high fat diet (HFD), respectively. During the last 4 weeks of treatment atorvastatin (Ator, 10mg/kg body weight/day) or control vehicle was administered via daily oral gavage. Blood lipids (total cholesterol, VLDL, LDL-C, HDL-C) and serum sphingolipids were compared among the groups. The expressions of hepatic and intestinal genes involved in cholesterol metabolism were analyzed by qRT-PCR. Alterations in the gut microbiota profile of mice with intact gut microbiome were examined using 16S RNA qRT-PCR. Results In CONV mice, HFD led to significantly increased blood LDL-C levels as compared with SCD (HFD: 36.8±1.4 mg/dl vs. SCD: 22.0±1.8 mg/dl; P<0.01). In CONV mice atorvastatin treatment significantly reduced blood LDL-C levels after HFD, whereas in ABS mice the LDL-C lowering effect of atorvastatin was markedly attenuated (CONV+HFD+Ator: 31.0±1.8 mg/dl vs. ABS+HFD+Ator: 46.4±3 mg/dl; P<0.01). A significant reduction in the abundance of several plasma lipids, in particular sphingolipids and glycerophospholipids upon atorvastatin treatment was observed in CONV mice, but not in ABS mice. The expressions of distinct hepatic and intestinal cholesterol-regulating genes (ldlr, srebp2, pcsk9 and npc1l1) upon atorvastatin treatment were significantly altered in gut microbiota depleted mice. In response to HFD a decrease in the relative abundance of the bacterial phyla Bacteroides and an increase in the relative abundance of Firmicutes was observed. The altered ratio between Bacteroides and Firmicutes in HFD fed mice was partly reversed upon atorvastatin treatment. Conclusions Our findings indicate a crucial role of the gut microbiome for the regulatory properties of atorvastatin on the serum lipidome and, in turn, support a critical impact of atorvastatin on the gut microbial composition. The results provide novel insights into potential microbiota related mechanisms underlying interindividual variation in modulation of the serum lipidome by statins, given interindividual differences in microbiome composition and function. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Heart Research Foundation

scholarly journals Gut Microbiome Alterations in Patients With Thyroid Nodules

2021 ◽  
Vol 11 ◽  
Author(s):  
Ang Li ◽  
Tiantian Li ◽  
Xinxin Gao ◽  
Hang Yan ◽  
Jingfeng Chen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Thyroid Nodules ◽  
Genome Wide Association Study ◽  
Adult Population ◽  
Lower Grade ◽  
High Grade ◽  
Microbial Composition ◽  
Thyroid Metabolism ◽  
Relative Abundances

Thyroid nodules are found in nearly half of the adult population. Accumulating evidence suggests that the gut microbiota plays an important role in thyroid metabolism, yet the association between gut microbiota capacity, thyroid nodules, and thyroid function has not been studied comprehensively. We performed a gut microbiome genome-wide association study in 196 patients with thyroid nodules and 283 controls by using whole-genome shotgun sequencing. We found that participants with high-grade thyroid nodules have decreased number of gut microbial species and gene families compared with those with lower grade nodules and controls. There are also significant alterations in the overall microbial composition in participants with high-grade thyroid nodules. The gut microbiome in participants with high-grade thyroid nodules is characterized by greater amino acid degradation and lower butyrate production. The relative abundances of multiple butyrate producing microbes are reduced in patients with high-grade thyroid nodules and the relative abundances of L-histidine metabolism pathways are associated with thyrotropin-releasing hormone. Our study describes the gut microbiome characteristics in thyroid nodules and a gut-thyroid link and highlight specific gut microbiota as a potential therapeutic target to regulate thyroid metabolism.

scholarly journals Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

2022 ◽  
Vol 8 ◽  
Author(s):  
Shuangyue Li ◽  
Georgios Kararigas
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Microbial Composition ◽  
Biological Sex ◽  
Technological Advances ◽  
Host Health ◽  
Health And Disease ◽  
And Function ◽  
Insight Into

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

scholarly journals Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation

2019 ◽  
Vol 7 (10) ◽  
pp. 456 ◽  
Author(s):  
Kaliyan Barathikannan ◽  
Ramachandran Chelliah ◽  
Momna Rubab ◽  
Eric Banan-Mwine Daliri ◽  
Fazle Elahi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Short Chain Fatty Acids ◽  
Genetic Profile ◽  
Fecal Transplantation ◽  
Intestinal Microbes ◽  
Prevalence Of Obesity ◽  
Future Direction ◽  
The Impact

The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.

scholarly journals The Effects of Glucosamine and Chondroitin Sulfate on Gut Microbial Composition: A Systematic Review of Evidence from Animal and Human Studies

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 294 ◽  
Author(s):  
Anna Shmagel ◽  
Ryan Demmer ◽  
Daniel Knights ◽  
Mary Butler ◽  
Lisa Langsetmo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Gut Microbiota ◽  
Chondroitin Sulfate ◽  
Gut Microbiome ◽  
Human Studies ◽  
Journal Articles ◽  
Microbial Composition ◽  
Microbiome Composition ◽  
Search Terms ◽  
Quality Evidence

Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus Bacteroides in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in Desulfovibrio piger species, an increase in Bacteroidales S24-7 family, and a decrease in Lactobacillus. We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.

scholarly journals The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice

2019 ◽  
Vol 5 (2) ◽  
pp. eaau8317 ◽  
Author(s):  
Peng Zheng ◽  
Benhua Zeng ◽  
Meiling Liu ◽  
Jianjun Chen ◽  
Junxi Pan ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Brain Function ◽  
Molecular Mechanisms ◽  
Diversity Index ◽  
Area Under The Curve ◽  
Healthy Controls ◽  
Microbial Composition ◽  
Germ Free ◽  
Α Diversity ◽  
Neurologic Function

Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mechanisms. The gut microbiome can modulate brain function and behaviors through the microbiota-gut-brain axis. Here, we found that unmedicated and medicated patients with SCZ had a decreased microbiome α-diversity index and marked disturbances of gut microbial composition versus healthy controls (HCs). Several unique bacterial taxa (e.g., Veillonellaceae and Lachnospiraceae) were associated with SCZ severity. A specific microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) enabled discriminating patients with SCZ from HCs with 0.769 area under the curve. Compared to HCs, germ-free mice receiving SCZ microbiome fecal transplants had lower glutamate and higher glutamine and GABA in the hippocampus and displayed SCZ-relevant behaviors similar to other mouse models of SCZ involving glutamatergic hypofunction. Together, our findings suggest that the SCZ microbiome itself can alter neurochemistry and neurologic function in ways that may be relevant to SCZ pathology.

scholarly journals Dysbiosis of gut microbiota and its correlation with dysregulation of cytokines in psoriasis patients

2021 ◽  
Author(s):  
Xinyue Zhang ◽  
Kun Guo ◽  
Linjing Shi ◽  
Ting Sun ◽  
Songmei Geng
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
High Throughput Sequencing ◽  
Interleukin 2 ◽  
Negative Relationship ◽  
Healthy Individuals ◽  
Microbial Composition ◽  
Microbiome Composition ◽  
The Relationship

Abstract Background: Psoriasis is an inflammatory skin disease associated with multiple comorbidities and substantially diminishes patients’ quality of life. The gut microbiome has become a hot topic in psoriasis as it has been shown to affect both allergy and autoimmunity diseases in recent studies. Our objective was to identify differences in the fecal microbial composition of patients with psoriasis compared with healthy individuals to unravel the microbiota profiling in this autoimmune disease.Results: We collected fecal samples from 30 psoriasis patients and 30 healthy controls, sequenced them by 16S rRNA high-throughput sequencing, and identified the gut microbial composition using bioinformatic analyses including Quantitative Insights into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Our results showed that different relative abundance of certain bacterial taxa between psoriasis patients and healthy individuals, including Faecalibacterium and Megamonas, were increased in patients with psoriasis. It’s also implicated that many cytokines act as main effect molecules in the pathology of psoriasis. We selected the inflammation-related indicators that were abnormal in psoriasis patients and found the microbiome variations were associated with the level of them, especially interleukin-2 receptor showed a positive relationship with Phascolarctobacterium and a negative relationship with the dialister. The relative abundance of Phascolarctobacterium and dialister can be regard as predictors of psoriasis activity. The correlation analysis based on microbiota and Inflammation-related indicators showed that microbiota dysbiosis might induce an abnormal immune response in psoriasis. Conclusions: We concluded that the gut microbiome composition in psoriasis patients has been altered markedly and provides evidence to understand the relationship between gut microbiota and psoriasis. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of psoriasis and whether the relationship between gut microbiota and cytokines was involved.

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