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

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.

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

Nutrients ◽

10.3390/nu13020690 ◽

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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2579. Impact on the Gut Microbiota of the Prolonged Antimicrobial Therapy in Patients with Bone and Joint Infection (BJI): Results From the OSIRIS Prospective Study in France

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2257 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S896-S896

Author(s):

Benoit Levast ◽

Cécile Batailler ◽

Cécile Pouderoux ◽

Lilia Boucihna ◽

Sébastien Lustig ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Joint Infection ◽

Surrogate Marker ◽

Generation Cephalosporin ◽

Fecal Microbiota ◽

Metagenomic Sequencing ◽

Gut Dysbiosis ◽

Prosthetic Joint ◽

The Impact

Abstract Background There is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not. Methods Multicentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation. Results Concerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI. Conclusion The impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation. Disclosures All authors: No reported disclosures.

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The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy

Frontiers in Oncology ◽

10.3389/fonc.2021.720842 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiangjun Liu ◽

Ye Cheng ◽

Dan Zang ◽

Min Zhang ◽

Xiuhua Li ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Gut Microbiome ◽

Fecal Microbiota Transplantation ◽

Checkpoint Inhibitors ◽

Fecal Microbiota ◽

Immune Homeostasis ◽

Gut Dysbiosis ◽

Underlying Mechanisms ◽

And Function

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.

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Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients

10.21203/rs.3.rs-54135/v1 ◽

2020 ◽

Author(s):

Zhaoqun Deng ◽

Fengqiong Liu ◽

Shanliang Ye ◽

Xin Zhu ◽

Xuesong He ◽

...

Keyword(s):

B Cells ◽

Gut Microbiota ◽

Post Infection ◽

Fecal Microbiota Transplantation ◽

Gastrointestinal Symptoms ◽

Fecal Microbiota ◽

Psychological Disorder ◽

Community Diversity ◽

General Distribution ◽

Gut Dysbiosis

Abstract Background: Gastrointestinal manifestations and gut dysbiosis are prevalent after SARS-CoV2 infection.With the continuously increasing number of infected cases, more attention should be paid to this particular population in post-infection recovery.cWe aimed to investigate the potential beneficial effect of FMT on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients. Results: Gastrointestinal and psychological disorder (45.5%) were observed in COVID-19 patients during post-infection recovery, improvement of which were observed after FMT. Most of the lab results including blood routine and blood biochemistry, within the normal range. The general distribution of 69 different types of lymphocytes differed between before and after FMT. FMT exert significant effect on B cells which was characterized as decreased naive B cell ( P =0.012) and increased memory B cells ( P = 0.001) and non-switched B cells ( P = 0.012).The microbial community richness indicated by OTUs number, observed species and Chao1 estimators was marginally increased after FMT, whereas the community diversity estimated by the Shannon and Simpson index showed no significant changes after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteriato (9.2%). FMT can partially restore the gutdysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteriato (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium , which were dominant genera in the human gut microbiota and were beneficial for human health, had significantly increased after FMT. Conclusions: Gastrointestinal and gut dysbiosis were observed in COVID-19 patients during post-infection recovery. FMT can improve the immune functionality, restore the gut microbiota, alleviate gastrointestinal disorders, and may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.

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Contribution of uremic dysbiosis to insulin resistance and sarcopenia

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa076 ◽

2020 ◽

Vol 35 (9) ◽

pp. 1501-1517 ◽

Cited By ~ 4

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.

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In Situ Profiling of the Three Dominant Phyla Within the Human Gut Using TaqMan PCR for Pre-Hospital Diagnosis of Gut Dysbiosis

International Journal of Molecular Sciences ◽

10.3390/ijms21061916 ◽

2020 ◽

Vol 21 (6) ◽

pp. 1916

Author(s):

Young Jae Jo ◽

Setu Bazie Tagele ◽

Huy Quang Pham ◽

YeonGyun Jung ◽

Jerald Conrad Ibal ◽

...

Keyword(s):

Gut Microbiota ◽

Emergency Services ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Human Gut ◽

Novel Therapy ◽

Emergency Situations ◽

Gut Dysbiosis ◽

Healthy Donors ◽

Periodic Monitoring

A microbial imbalance called dysbiosis leads to inflammatory bowel disease (IBD), which can include ulcerative colitis (UC). Fecal microbiota transplantation (FMT), a novel therapy, has recently been successful in treating gut dysbiosis in UC patients. For the FMT technique to be successful, the gut microbiota of both the healthy donors and UC patients must be characterized. For decades, next-generation sequencing (NGS) has been used to analyze gut microbiota. Despite the popularity of NGS, the cost and time constraints make it difficult to use in emergency services and activities related to the periodic monitoring of microbiota profile alterations. Hence, in this study, we developed a multiplex TaqMan qPCR assay (MTq-PCR) with novel probes to simultaneously determine the relative proportions of the three dominant microbial phyla in the human gut: Bacteroidetes, Firmicutes, and Proteobacteria. The relative proportions of the three phyla in fecal samples of either healthy volunteers or UC patients were similar when assessed NGS and the MTq-PCR. Thus, our MTq-PCR assay could be a practical microbiota profiling alternative for diagnosing and monitoring gut dysbiosis in UC patients during emergency situations, and it could have a role in screening stool from potential FMT donors.

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

Translational Psychiatry ◽

10.1038/s41398-020-01024-9 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 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.

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Fecal Microbiota Transplantation in Patients with HBV Infection or Other Chronic Liver Diseases: Update on Current Knowledge and Future Perspectives

Journal of Clinical Medicine ◽

10.3390/jcm10122605 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2605

Author(s):

Mattia Paratore ◽

Francesco Santopaolo ◽

Giovanni Cammarota ◽

Maurizio Pompili ◽

Antonio Gasbarrini ◽

...

Keyword(s):

Liver Disease ◽

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Current Knowledge ◽

Fecal Microbiota ◽

Clinical Settings ◽

Gut Dysbiosis ◽

Bidirectional Relationship ◽

Cirrhotic Patients ◽

Gut Microbiota Composition

Liver disease and gut dysbiosis are strictly associated, and the pathophysiology of this bidirectional relationship has recently been the subject of several investigations. Growing evidence highlights the link between gut microbiota composition, impairment of the gut-liver axis, and the development or progression of liver disease. Therefore, the modulation of gut microbiota to maintain homeostasis of the gut-liver axis could represent a potential instrument to halt liver damage, modify the course of liver disease, and improve clinical outcomes. Among all the methods available to achieve this purpose, fecal microbiota transplantation (FMT) is one of the most promising, being able to directly reshape the recipient’s gut microbial communities. In this review, we report the main characteristics of gut dysbiosis and its pathogenetic consequences in cirrhotic patients, discussing the emerging data on the application of FMT for liver disease in different clinical settings.

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P163 DYSREGULATED MICROBIAL METABOLISM IN ULCERATIVE COLITIS INCREASES THE RISK OF CLOSTRIDIODES DIFFICILE INFECTION

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.102 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S40-S40

Author(s):

Hiroko Kitamoto ◽

Peter Higgins ◽

Vincent Young ◽

Nobuhiko Kamada

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Critical Role ◽

Microbial Metabolism ◽

Fecal Microbiota ◽

Host Susceptibility ◽

Gut Dysbiosis ◽

Clostridioides Difficile ◽

Increased Susceptibility

Abstract Clostridioides difficile infection (CDI) is recognized as a major clinical complication in patients with ulcerative colitis (UC). However, the mechanism associated with increased susceptibility to C. difficile in UC patients remains poorly understood. Given the evidence that the gut microbiota plays a critical role in the prevention of CDI and that gut microbiota is perturbed in UC patients, we hypothesized that UC-associated gut dysbiosis contributes to the increased susceptibility of patients to CDI. To address this hypothesis, we employed the human microbiota-associated (HMA) mouse model. Germ-free mice were colonized with the gut microbiotas isolated from either UC patients or healthy control (HC) subjects. Utilizing this model, we have found that UC-HMA mice are susceptible to C. difficile, while HC-HMA mice are completely protected. An isogenic mutant C. difficile strain, which lacks the succinate utilization operon, exhibited impaired colonization to UC-HMA mice, indicating that succinate is a key metabolite that promotes the colonization of C. difficile in UC-HMA mice. Restoration of healthy microbiotas by fecal microbiota transplantation (FMT) reduced luminal concentration of succinate in UC-HMA mice, thereby rendering the mice protective against CDI. The abundance of succinate-consuming bacteria likely regulates the availability of luminal succinate. We found that host mucus/epithelial N-glycosylation plays a crucial role in the growth of succinate-consuming bacteria in the gut. The expression of N-glycosylation–related enzymes were reduced in UC patients, which may lead to the gut dysbiosis with decreased succinate-consuming bacteria and increased luminal succinate. Taken together, impaired host N-glycosylation in UC induces gut dysbiosis and subsequent dysregulation of gut microbial metabolism. The impaired microbial metabolic activities - reduced succinate utilization - increases host susceptibility to C. difficile.

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Gut-testis axis: microbiota-(n-3) PUFA improving semen quality in type 1 diabetes

10.1101/2021.11.24.469971 ◽

2021 ◽

Author(s):

Yong Zhao ◽

Yanan Hao ◽

Yanni Feng ◽

Xiaowei Yan ◽

Liang Chen ◽

...

Keyword(s):

Type 1 Diabetes ◽

Gut Microbiota ◽

Semen Quality ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Reproductive Age ◽

Beneficial Effects ◽

Gut Dysbiosis ◽

Alginate Oligosaccharide

Gut dysbiosis and type 1 diabetes (T1D) are closely related, and gut dysbiosis and male infertility are correlated, too. Moreover, most male T1D patients are of active reproductive age. Therefore, it is crucial to explore possible means for improving their semen quality. Here, we found that fecal microbiota transplantation (FMT) from alginate oligosaccharide (AOS) improved gut microbiota (A10-FMT) significantly decreased blood glucose and glycogen, and increased semen quality in streptozotocin-induced T1D subjects. A10-FMT improved T1D-disturbed gut microbiota, especially the increase in small intestinal lactobacillus, and blood and testicular metabolome to produce n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to ameliorate spermatogenesis and semen quality. Moreover, A10-FMT can improve spleen and liver function to strengthen the systemic environment for sperm development. FMT from gut microbiota of control animals (Con-FMT) produced some beneficial effects; however, to a smaller extent. Thus, AOS improved gut microbiota may be a useful protocol for improving semen quality and male fertility in T1D patients.

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