scholarly journals Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Haiyang Wang ◽  
Lanxiang Liu ◽  
Xuechen Rao ◽  
Benhua Zeng ◽  
Ying Yu ◽  
...  
Keyword(s):  
Mental Disorders ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Neuronal Function ◽  
Neurotransmitter System ◽  
Metabolomic Profiling ◽  
Specific Pathogen ◽  
New Perspective ◽  
Gut Microbiota Dysbiosis

Abstract The dysbiosis of gut microbiota is an important environmental factor that can induce mental disorders, such as depression, through the microbiota–gut–brain axis. However, the underlying pathogenic mechanisms are complex and not completely understood. Here we utilized mass spectrometry to identify the global phosphorylation dynamics in hippocampus tissue in germ-free mice and specific pathogen-free mice (GF vs SPF), fecal microbiota transplantation (FMT) model (“depression microbiota” and the “healthy microbiota” recipient mice). As a result, 327 phosphosites of 237 proteins in GF vs SPF, and 478 phosphosites of 334 proteins in “depression microbiota” vs “healthy microbiota” recipient mice were identified as significant. These phosphorylation dysregulations were consistently associated with glutamatergic neurotransmitter system disturbances. The FMT mice exhibited disturbances in lipid metabolism and amino acid metabolism in both the periphery and brain through integrating phosphoproteomic and metabolomic analysis. Moreover, CAMKII-CREB signaling pathway, in response to these disturbances, was the primary common perturbed cellular process. In addition, we demonstrated that the spliceosome, never directly implicated in mental disorders previously, was a substantially neuronal function disrupted by gut microbiota dysbiosis, and the NCBP1 phosphorylation was identified as a novel pathogenic target. These results present a new perspective to study the pathologic mechanisms of gut microbiota dysbiosis related depression and highlight potential gut-mediated therapies for depression.

scholarly journals Longitudinal Analyses Reveal That Aging-related Alterations in the Intestinal Environment Lead to Gut Dysbiosis With the Potential to Induce Obesity

2020 ◽  
Author(s):  
Yumiko Nakanishi ◽  
Ryouko Nozu ◽  
Masami Ueno ◽  
Kyoji Hioki ◽  
Chiharu Ishii ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Middle Age ◽  
Fecal Microbiota Transplantation ◽  
Fold Increase ◽  
Fecal Microbiota ◽  
Whole Body ◽  
Cellular Functions ◽  
Intestinal Environment ◽  
Gut Dysbiosis ◽  
Specific Pathogen

Abstract Background: Aging is a progressive decline of cellular functions that ultimately affects whole-body homeostasis. Alterations in the gut microbiota associated with aging have been reported, however the molecular basis of the relationships between host aging and the gut microbiota is poorly understood.Result: By using longitudinal microbiome and metabolome characterization, we show that the aging-related alterations in the intestinal environment lead to gut dysbiosis with a potential to induce obesity in mice. In middle-age mice, we observed more than a 2-fold increase in fecal carbohydrates derived from dietary polysaccharides and a significant reduction of gut microbial diversity resembling the microbiota characteristic of obese mice. Consistently, fecal microbiota transplantation from middle-age specific pathogen-free (SPF) mice into young germ-free (GF) mice resulted in increased weight gain and impaired glucose tolerance.Conclusion: Our findings provide new insights into the relationships between host aging and gut dysbiosis and may contribute to the development of a possible solution to aging-related obesity.

scholarly journals Effects from diet-induced gut microbiota dysbiosis and obesity can be ameliorated by fecal microbiota transplantation: A multiomics approach

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0218143 ◽  
Author(s):  
Maria Guirro ◽  
Andrea Costa ◽  
Andreu Gual-Grau ◽  
Pol Herrero ◽  
Helena Torrell ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Gut Microbiota Dysbiosis

scholarly journals Obesity-induced gut microbiota dysbiosis can be ameliorated by fecal microbiota transplantation: a multiomics approach

2019 ◽  
Author(s):  
Maria Guirro ◽  
Andrea Costa ◽  
Andreu Gual-Grau ◽  
Pol Herrero ◽  
Helena Torrell ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Fecal Microbiota Transplantation ◽  
Obese Subject ◽  
Fecal Microbiota ◽  
Obesity Therapy ◽  
Treatment Of Obesity ◽  
And Function ◽  
Hypercaloric Diet ◽  
Gut Microbiota Dysbiosis

AbstractObesity and its comorbidities are currently considered an epidemic, and the involved pathophysiology is well studied. Recently, the gut microbiota has emerged as a new potential therapeutic target for the treatment of obesity. Diet and antibiotics are known to play crucial roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the manipulation of gut microbiota may represent a strategy for obesity treatment. Fecal microbiota transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese subject, has aroused interest as an effective approach for the treatment of obesity. To determine its success, a multiomics approach was used that combined metagenomics and metaproteomics to study microbiota composition and function.To do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our results showed that a high-fat diet induces changes in microbiota biodiversity and alters its function in the host. Moreover, we found that antibiotics depleted the microbiota enough to reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as an obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the microbiota balance, which restored normal functioning and alleviated microbiota disruption.

scholarly journals Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Donglin Du ◽  
Wei Tang ◽  
Chao Zhou ◽  
Xiaochuan Sun ◽  
Zhengqiang Wei ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Methionine Sulfoxide Reductase ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Rat Serum ◽  
Gut Microbiota Dysbiosis

Background. Traumatic brain injury (TBI) can induce persistent fluctuation in the gut microbiota makeup and abundance. The present study is aimed at determining whether fecal microbiota transplantation (FMT) can rescue microbiota changes and ameliorate neurological deficits after TBI in rats. Methods. A controlled cortical impact (CCI) model was used to simulate TBI in male Sprague-Dawley rats, and FMT was performed for 7 consecutive days. 16S ribosomal RNA (rRNA) sequencing of fecal samples was performed to analyze the effects of FMT on gut microbiota. Modified neurological severity score and Morris water maze were used to evaluate neurobehavioral functions. Metabolomics was used to screen differential metabolites from the rat serum and ipsilateral brains. The oxidative stress indices were measured in the brain. Results. TBI induced significance changes in the gut microbiome, including the alpha- and beta-bacterial diversity, as well as the microbiome composition at 8 days after TBI. On the other hand, FMT could rescue these changes and relieve neurological deficits after TBI. Metabolomics results showed that the level of trimethylamine (TMA) in feces and the level of trimethylamine N-oxide (TMAO) in the ipsilateral brain and serum was increased after TBI, while FMT decreased TMA levels in the feces, and TMAO levels in the ipsilateral brain and serum. Antioxidant enzyme methionine sulfoxide reductase A (MsrA) in the ipsilateral hippocampus was decreased after TBI but increased after FMT. In addition, FMT elevated SOD and CAT activities and GSH/GSSG ratio and diminished ROS, GSSG, and MDA levels in the ipsilateral hippocampus after TBI. Conclusions. FMT can restore gut microbiota dysbiosis and relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI.

scholarly journals Gut Microbiota Was Involved in the Process of Liver Injury During Intra-Abdominal Hypertension

2021 ◽  
Vol 12 ◽  
Author(s):  
Zeyu Zhao ◽  
Zhengchang Guo ◽  
Zhengliang Yin ◽  
Yue Qiu ◽  
Bo Zhou
Keyword(s):  
Liver Injury ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Intestinal Damage ◽  
Abdominal Hypertension ◽  
Portal Veins ◽  
The Relationship ◽  
Abdominal Compartment ◽  
Gut Microbiota Dysbiosis

Background: Intestinal damage caused by intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) can lead to the ectopic gut microbiota, which can contribute to liver injury via portal veins. Therefore, it is speculated that gut microbiota disorder caused by IAH/ACS may result in liver injury. The relationship between gut microbiota and IAH/ACS-related liver injury was investigated in this study.Methods: A model of IAH was established in rats, and 16S rRNA sequencing was analyzed for gut microbiota in the feces of rats. The elimination of gut microbiota was completed by antibiotics gavage, and fecal microbiota transplantation (FMT) was used to change the composition of gut microbiota in rats.Results: In addition to the traditional cause of liver blood vessel compression, liver injury caused by IAH was also associated with gut microbiota dysbiosis. Gut microbiota clearance can relieve liver injury caused by IAH, while FMT from IAH-intervened rats can aggravate IAH-related liver injury.Conclusion: The gut microbiota was one of the most important factors contributing to the IAH-related liver injury, and the JNK/p38 signaling pathway was activated in this process.

scholarly journals Contribution of uremic dysbiosis to insulin resistance and sarcopenia

2020 ◽  
Vol 35 (9) ◽  
pp. 1501-1517 ◽  
Author(s):  
Kiyotaka Uchiyama ◽  
Shu Wakino ◽  
Junichiro Irie ◽  
Junki Miyamoto ◽  
Ayumi Matsui ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Normal Diet ◽  
Fermentation Products ◽  
Bacterial Fermentation ◽  
Junction Protein ◽  
Specific Pathogen ◽  
And Control

Abstract Background Chronic kidney disease (CKD) leads to insulin resistance (IR) and sarcopenia, which are associated with a high mortality risk in CKD patients; however, their pathophysiologies remain unclear. Recently, alterations in gut microbiota have been reported to be associated with CKD. We aimed to determine whether uremic dysbiosis contributes to CKD-associated IR and sarcopenia. Methods CKD was induced in specific pathogen-free mice via an adenine-containing diet; control animals were fed a normal diet. Fecal microbiota transplantation (FMT) was performed by oral gavage in healthy germ-free mice using cecal bacterial samples obtained from either control mice (control-FMT) or CKD mice (CKD-FMT). Vehicle mice were gavaged with sterile phosphate-buffered saline. Two weeks after inoculation, mice phenotypes, including IR and sarcopenia, were evaluated. Results IR and sarcopenia were evident in CKD mice compared with control mice. These features were reproduced in CKD-FMT mice compared with control-FMT and vehicle mice with attenuated insulin-induced signal transduction and mitochondrial dysfunction in skeletal muscles. Intestinal tight junction protein expression and adipocyte sizes were lower in CKD-FMT mice than in control-FMT mice. Furthermore, CKD-FMT mice showed systemic microinflammation, increased concentrations of serum uremic solutes, fecal bacterial fermentation products and elevated lipid content in skeletal muscle. The differences in gut microbiota between CKD and control mice were mostly consistent between CKD-FMT and control-FMT mice. Conclusions Uremic dysbiosis induces IR and sarcopenia, leaky gut and lipodystrophy.

scholarly journals Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhe Zhao ◽  
Jingwen Ning ◽  
Xiu-qi Bao ◽  
Meiyu Shang ◽  
Jingwei Ma ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gut Microbiota ◽  
Signaling Pathway ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Motor Deficits ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway ◽  
The Brain ◽  
Gut Microbiota Dysbiosis

Abstract Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies. Here, in this study, we established a chronic rotenone-induced PD mouse model to evaluate the protective effects of FMT treatment on PD and to explore the underlying mechanisms, which also proves the involvement of gut microbiota dysbiosis in PD pathogenesis via the microbiota-gut-brain axis. Results We demonstrated that gut microbiota dysbiosis induced by rotenone administration caused gastrointestinal function impairment and poor behavioral performances in the PD mice. Moreover, 16S RNA sequencing identified the increase of bacterial genera Akkermansia and Desulfovibrio in fecal samples of rotenone-induced mice. By contrast, FMT treatment remarkably restored the gut microbial community, thus ameliorating the gastrointestinal dysfunctions and the motor deficits of the PD mice. Further experiments revealed that FMT administration alleviated intestinal inflammation and barrier destruction, thus reducing the levels of systemic inflammation. Subsequently, FMT treatment attenuated blood-brain barrier (BBB) impairment and suppressed neuroinflammation in the substantia nigra (SN), which further decreased the damage of dopaminergic neurons. Additional mechanistic investigation discovered that FMT treatment reduced lipopolysaccharide (LPS) levels in the colon, the serum, and the SN, thereafter suppressing the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products both in the SN and the colon. Conclusions Our current study demonstrates that FMT treatment can correct the gut microbiota dysbiosis and ameliorate the rotenone-induced PD mouse model, in which suppression of the inflammation mediated by the LPS-TLR4 signaling pathway both in the gut and the brain possibly plays a significant role. Further, we prove that rotenone-induced microbiota dysbiosis is involved in the genesis of PD via the microbiota-gut-brain axis.

scholarly journals Proteomics analysis of the gut–brain axis in a gut microbiota-dysbiosis model of depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yiyun Liu ◽  
Haiyang Wang ◽  
Siwen Gui ◽  
Benhua Zeng ◽  
Juncai Pu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Protein Expression ◽  
Fecal Microbiota Transplantation ◽  
Enrichment Analysis ◽  
Fecal Microbiota ◽  
Proteomics Approach ◽  
Stress Models ◽  
Protein Modules ◽  
Coexpression Network Analysis ◽  
Gut Microbiota Dysbiosis

AbstractMajor depressive disorder (MDD) is a serious mental illness. Increasing evidence from both animal and human studies suggested that the gut microbiota might be involved in the onset of depression via the gut–brain axis. However, the mechanism in depression remains unclear. To explore the protein changes of the gut–brain axis modulated by gut microbiota, germ-free mice were transplanted with gut microbiota from MDD patients to induce depression-like behaviors. Behavioral tests were performed following fecal microbiota transplantation. A quantitative proteomics approach was used to examine changes in protein expression in the prefrontal cortex (PFC), liver, cecum, and serum. Then differential protein analysis and weighted gene coexpression network analysis were used to identify microbiota-related protein modules. Our results suggested that gut microbiota induced the alteration of protein expression levels in multiple tissues of the gut–brain axis in mice with depression-like phenotype, and these changes of the PFC and liver were model specific compared to chronic stress models. Gene ontology enrichment analysis revealed that the protein changes of the gut–brain axis were involved in a variety of biological functions, including metabolic process and inflammatory response, in which energy metabolism is the core change of the protein network. Our data provide clues for future studies in the gut–brain axis on protein level and deepen the understanding of how gut microbiota cause depression-like behaviors.

scholarly journals Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 734
Author(s):  
Gwangbeom Heo ◽  
Yunna Lee ◽  
Eunok Im
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Inflammatory Mediators ◽  
Tumor Metastasis ◽  
Intestinal Tract ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Therapeutic Interventions ◽  
Potential Therapeutic Target ◽  
Necrosis Factor

Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.

scholarly journals Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 690
Author(s):  
Umair Shabbir ◽  
Muhammad Sajid Arshad ◽  
Aysha Sameen ◽  
Deog-Hwan Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Dietary Habits ◽  
Inflammatory Responses ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Gut Dysbiosis ◽  
Dynamic Population

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

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