scholarly journals The gut microbiome in tuberculosis susceptibility and treatment response: guilty or not guilty?

2019 ◽  
Vol 77 (8) ◽  
pp. 1497-1509 ◽  
Author(s):  
Osagie A. Eribo ◽  
Nelita du Plessis ◽  
Mumin Ozturk ◽  
Reto Guler ◽  
Gerhard Walzl ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Gut Microbiota ◽  
Treatment Response ◽  
Gut Microbiome ◽  
Underlying Mechanism ◽  
Host Immunity ◽  
Disease Development ◽  
Healthy Individuals ◽  
Immune Pathways ◽  
Increased Susceptibility

AbstractAlthough tuberculosis (TB) is a curable disease, it remains the foremost cause of death from a single pathogen. Globally, approximately 1.6 million people died of TB in 2017. Many predisposing factors related to host immunity, genetics and the environment have been linked to TB. However, recent evidence suggests a relationship between dysbiosis in the gut microbiome and TB disease development. The underlying mechanism(s) whereby dysbiosis in the gut microbiota may impact the different stages in TB disease progression, are, however, not fully explained. In the wake of recently emerging literature, the gut microbiome could represent a potential modifiable host factor to improve TB immunity and treatment response. Herein, we summarize early data detailing (1) possible association between gut microbiome dysbiosis and TB (2) the potential for the use of microbiota biosignatures to discriminate active TB disease from healthy individuals (3) the adverse effect of protracted anti-TB antibiotics treatment on gut microbiota balance, and possible link to increased susceptibility to Mycobacterium tuberculosis re-infection or TB recrudescence following successful cure. We also discuss immune pathways whereby the gut microbiome could impact TB disease and serve as target for clinical manipulation.

scholarly journals Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review

2020 ◽  
Author(s):  
Chengliang Huang ◽  
Meizhang Li ◽  
Ben Liu ◽  
Huanbo Zhu ◽  
Qun Dai ◽  
...  
Keyword(s):  
Treatment Response ◽  
Solid Tumors ◽  
Gut Microbiome ◽  
Negative Impact ◽  
Checkpoint Inhibitors ◽  
Antibiotic Use ◽  
Underlying Mechanism ◽  
Lifestyle Factor ◽  
Therapeutic Outcomes

Abstract Background: Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet.Methods: A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included.Results: At the phylum level, patients who had enriched abundance in Firmicutes and Verrucomicrobia almost universally had better response from ICIs, whereas those who were enriched in Proteobacteria universally presented with unfavorable outcome. Mixed correlations were observed for Bacteroidetes in relating to treatment response. Regarding the AEs, Firmicutes correlated to higher incidence whereas Bacteroidetes were clearly associated with less occurrence. Interestingly, across various solid tumors, majority of the studies suggested a negative association of antibiotic use with clinical response from ICIs, especially within 1-2 month prior to the initiation of ICIs. Finally, we observed a significant correlation of plant-based diet in relating to the enrichment of “ICI-favoring” gut microbiome (P = 0.0476).Conclusions: Gut microbiome may serve as a novel modifiable biomarker for both the treatment response and AEs of ICIs across various solid tumors. Further study is needed to understand the underlying mechanism, minimize the negative impact of antibiotics on ICIs, and gain insight regarding the role of diet so that this important lifestyle factor can be harnessed to improve the therapeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome.

Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21024-e21024
Author(s):  
Justin Chau ◽  
Meeta Yadav ◽  
Ben Liu ◽  
Muhammad Furqan ◽  
Qun Dai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Treatment Response ◽  
Gut Microbiome ◽  
Operational Taxonomic Unit ◽  
Geographic Region ◽  
Organ Function ◽  
Immune Mediated ◽  
Α Diversity ◽  
Clinical Trial Information

e21024 Background: Though the gut microbiome has been associated with immunotherapy (ICI) efficacy in certain cancers, similar correlations between microbiomes at other body sites with treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs have not been made. We designed a prospective cohort study conducted from 2018-2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Methods: Patients with histopathologically confirmed, unresectable/advanced/metastatic LC planned to undergo ICI-based therapy were enrolled between September 2018 and June 2019. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Nasal, buccal and gut microbiome samples were obtained prior to ICI initiation, at development of irAEs, improvement of irAEs to grade 1 or less, and at disease progression. 16S rRNA sequenced data was mapped to the SILVA 13.2 database; operational taxonomic unit clusters were analyzed using MicrobiomeAnalyst and METAGENassist. Results: 37 patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium ( p = 0.001) and Desulfovibrio ( p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales ( p = 0.018) but reduced Rikenellaceae ( p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. Conclusions: This pilot study identified significant differences in the gut microbiome between HC and LC patients, and correlates specific bacterial genera to ICI response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. Clinical trial information: NCT03688347.

scholarly journals Altered diversity and composition of gut microbiota in Wilson's disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiangsheng Cai ◽  
Lin Deng ◽  
Xiaogui Ma ◽  
Yusheng Guo ◽  
Zhiting Feng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Healthy Individuals ◽  
Lower Abundance ◽  
Rrna Sequencing ◽  
Healthy Control ◽  
The Impact ◽  
Bacterial Groups

AbstractWilson’s disease (WD) is an autosomal recessive inherited disorder of chronic copper toxicosis with high mortality and disability. Recent evidence suggests a correlation between dysbiosis in gut microbiome and multiple diseases such as genetic and metabolic disease. However, the impact of intestinal microbiota polymorphism in WD have not been fully elaborated and need to be explore for seeking some microbiota benefit for WD patients. In this study, the 16S rRNA sequencing was performed on fecal samples from 14 patients with WD and was compared to the results from 16 healthy individuals. The diversity and composition of the gut microbiome in the WD group were significantly lower than those in healthy individuals. The WD group presented unique richness of Gemellaceae, Pseudomonadaceae and Spirochaetaceae at family level, which were hardly detected in healthy controls. The WD group had a markedly lower abundance of Actinobacteria, Firmicutes and Verrucomicrobia, and a higher abundance of Bacteroidetes, Proteobacteria, Cyanobacteria and Fusobacteria than that in healthy individuals. The Firmicutes to Bacteroidetes ratio in the WD group was significantly lower than that of healthy control. In addition, the functional profile of the gut microbiome from WD patients showed a lower abundance of bacterial groups involved in the host immune and metabolism associated systems pathways such as transcription factors and ABC-type transporters, compared to healthy individuals. These results implied dysbiosis of gut microbiota may be influenced by the host metabolic disorders of WD, which may provide a new understanding of the pathogenesis and new possible therapeutic targets for WD.

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.

Antrodin A from Antrodia camphorata modulates the gut microbiome and liver metabolome in mice exposed to acute alcohol intake

2021 ◽  
Vol 12 (7) ◽  
pp. 2925-2937
Author(s):  
Zhenwei Yi ◽  
Xiaofeng Liu ◽  
Lihong Liang ◽  
Guangqiang Wang ◽  
Zhiqiang Xiong ◽  
...  
Keyword(s):  
Liver Injury ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Alcohol Intake ◽  
Underlying Mechanism ◽  
Antrodia Camphorata ◽  
Hepatoprotective Effects

In this study, we investigated the hepatoprotective effects of AdA and the underlying mechanism at the liver metabolomics and gut microbiota levels under alcohol-induced liver injury conditions.

scholarly journals Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis

2020 ◽  
Vol 134 (12) ◽  
pp. 1521-1535 ◽  
Author(s):  
Xinhuan Su ◽  
Ying Zhao ◽  
Yang Li ◽  
Shizhan Ma ◽  
Zhe Wang
Keyword(s):  
Gut Microbiota ◽  
Thyroid Function ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Characteristic Curve ◽  
Intestinal Flora ◽  
Intestinal Bacteria ◽  
Primary Hypothyroidism ◽  
Receiver Operator Characteristic Curve ◽  
Healthy Individuals

Abstract Background Previous studies have shown that the gut microbiome is associated with thyroid diseases, including Graves’ disease, Hashimoto's disease, thyroid nodules, and thyroid cancer. However, the association between intestinal flora and primary hypothyroidism remains elusive. We aimed to characterize gut microbiome in primary hypothyroidism patients. Methods Fifty-two primary hypothyroidism patients and 40 healthy controls were recruited. The differences in gut microbiota between the two groups were analyzed by 16S rRNA sequencing technology. Fecal microbiota transplantation (FMT) was performed in mice using flora from both groups; changes in thyroid function were then assessed in the mice. Results There were significant differences in α and β diversities of gut microbiota between primary hypothyroidism patients and healthy individuals. The random forest analysis indicated that four intestinal bacteria (Veillonella, Paraprevotella, Neisseria, and Rheinheimera) could distinguish untreated primary hypothyroidism patients from healthy individuals with the highest accuracy; this was confirmed by receiver operator characteristic curve analysis. The short chain fatty acid producing ability of the primary hypothyroidism patients’ gut was significantly decreased, which resulted in the increased serum lipopolysaccharide (LPS) levels. The FMT showed that mice receiving the transplant from primary hypothyroidism patients displayed decreased total thyroxine levels. Conclusions Our study suggests that primary hypothyroidism causes changes in gut microbiome. In turn, an altered flora can affect thyroid function in mice. These findings could help understand the development of primary hypothyroidism and might be further used to develop potential probiotics to facilitate the adjuvant treatment of this disease.

scholarly journals Altered Diversity and Composition of Gut Microbiota in Wilson's disease

2020 ◽  
Author(s):  
Xiangsheng Cai ◽  
Lin Deng ◽  
Xiaogui Ma ◽  
Yusheng Guo ◽  
Zhiting Feng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Healthy Individuals ◽  
Lower Abundance ◽  
Rrna Sequencing ◽  
Healthy Control ◽  
The Impact ◽  
Bacterial Groups

Abstract Background: Wilson’s disease (WD) is a rare autosomal recessive inherited disorder of chronic copper toxicosis with high mortality and disability. Recent evidence suggests a correlation between dysbiosis in the gut microbiome and metabolic disease. Therefore, the impact of intestinal microbiota polymorphism in WD need to be explore for seeking some microbiota benefit for WD patients. Methods: In this study, the 16S rRNA sequencing was performed on fecal samples from 14 patients with WD and were compared to the results from 16 healthy individuals. The diversity and composition of the gut microbiome in the WD group were significantly lower than those in healthy individuals. Results: The WD group presented unique richness of Gemellaceae , Pseudomonadaceae and Spirochaetaceae at family level in WD group, which were hardly detected in healthy controls The WD group had a markedly lower abundance of Acidobacteria , Firmicutes and Verrucomicrobia , and a higher abundance of Bacteroidet es, Proteobacteria , Cyanobacteria and Fusobacteria than that in healthy individuals. The Firmicutes to Bacteroidetes ratio in the WD group was significantly lower than that of healthy control. The functional profile of the gut microbiome from WD patients showed a lower abundance of bacterial groups involved in the pathways of transcription factors and ABC-type transporters, compared to healthy individuals. The dysbiosis of gut microbiota may be influenced by the host metabolic disorders of WD such as signaling pathway of ABC-type transporters and multiple metabolic modules. Conclusions: This study provides a new understanding of the pathogenesis of WD and new possible therapeutic targets.

Interactions between helicobacter-induced inflammation acute changes in the gut microbiota, and colorectal cancer in Smad3-/- mice

2020 ◽  
Author(s):  
◽  
Annie E. Wolfie
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Disease Severity ◽  
Community Dynamics ◽  
Inflammatory Diseases ◽  
Disease Incidence ◽  
Severe Disease ◽  
Underlying Mechanism ◽  
Post Inoculation ◽  
Disease Development

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI--COLUMBIA AT REQUEST OF AUTHOR.] Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for 551,269 deaths in 2018 alone. One subset of CRC, colitis associated CRC (CAC), develops as a sequela to chronic inflammatory diseases of the bowel. The underlying mechanism of CAC is poorly understood, but prognosis is poor due to difficulty of detection. Surveillance strategies are invasive and expensive. Risk factors of CAC include inflammatory bowel disease (IBD), diet, smoking, environment, and obesity--all of which impact or are impacted by the gut microbiota (GM), making the GM a prime target for understanding the etiology of CAC in order to develop preventative measures. Using the Smad3-/- CAC model, which requires inoculation of pathobiont Helicobacter spp., we tested the ability of the Th17-enhancing commensal Candidatus Savagella, more commonly denoted as Segmented Filamentous Bacteria (SFB), to influence the incidence and severity of CAC. To document the composition of the gut microbiota during CRC development and identify taxa associated with disease, fecal samples were collected before and throughout disease development and characterized via 16S rRNA sequencing. While there were no significant SFB-dependent effects on disease incidence or severity, SFB were found to exert a sex-dependent protective effect in male mice. Furthermore, SFB stabilized the GM against Helicobacter-induced changes post inoculation, resulting in a shift in disease association from Helicobacter spp. to Escherichia coli. These data support sex-dependent SFB-mediated effects on CRC risk, and highlight the complex community dynamics within the GM during exposure to inflammatory pathobionts. In order to artificially modulate disease severity, we repeated the above experiments using Smad3-/- mice rederived onto different GM backgrounds, using a technique called complex microbiota targeted rederivation (CMTR). Smad3-/- mice harboring distinct GM profiles termed GM1, GM2, and GM4 were similarly inoculated with Helicobacter spp. and followed longitudinally through disease development or lack thereof. We hypothesized that GM1 and 2 would develop the most severe disease, due to lack of richness and diversity. There was no difference in disease penetrance between the GM profiles, and no pre-disposing GM profile was found at pre-inoculation or early timepoints. However, GM2 developed greater disease severity than GM1 and GM4. Looking at static and dynamic differences between CRC- and CRC+ groups of each GM revealed OTUs, genera, and families which differed in disease development. Network construction analysis using overlapping timepoints from early to late, revealed that overall CRC+ bacterial communities had fewer connections than their CRC- counterparts. This was most striking in GM2 CRC+, which could account for the increased disease severity in this GM profile.

scholarly journals Microbial imbalance in inflammatory bowel disease patients at different taxonomic levels

Gut Pathogens ◽  
2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Mohammad Tauqeer Alam ◽  
Gregory C. A. Amos ◽  
Andrew R. J. Murphy ◽  
Simon Murch ◽  
Elizabeth M. H. Wellington ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Gut Microbiome ◽  
Global Scale ◽  
Rrna Gene ◽  
Healthy Individuals ◽  
Bacterial Phyla ◽  
Inflammatory Bowel ◽  
Bacterial Groups

Abstract Background Inflammatory bowel disease (IBD), is a debilitating group of chronic diseases including Crohn’s Disease (CD) and ulcerative colitis (UC), which causes inflammation of the gut and affects millions of people worldwide. At different taxonomic levels, the structure of the gut microbiota is significantly altered in IBD patients compared to that of healthy individuals. However, it is unclear how these IBD-affected bacterial groups are related to other common bacteria in the gut, and how they are connected across different disease conditions at the global scale. Results In this study, using faecal samples from patients with IBD, we show through diversity analysis of the microbial community structure based on the 16S rRNA gene that the gut microbiome of IBD patients is less diverse compared to healthy individuals. Furthermore, we have identified which bacterial groups change in abundance in both CD and UC compared to healthy controls. A substantial imbalance was observed across four major bacterial phyla including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria, which together constitute > 98% of the gut microbiota. Next, we reconstructed a bacterial family co-abundance network based on the correlation of abundance profiles obtained from the public gut microbiome data of > 22,000 samples of faecal and gut biopsies taken from both diseased and healthy individuals. The data was compiled using the EBI metagenomics database (Mitchell et al. in Nucleic Acids Res 46:D726–D735, 2018). By mapping IBD-altered bacterial families to the network, we show that the bacterial families which exhibit an increased abundance in IBD conditions are not well connected to other groups, implying that these families generally do not coexist together with common gut organisms. Whereas, the bacterial families whose abundance is reduced or did not change in IBD conditions compared to healthy conditions are very well connected to other bacterial groups, suggesting they are highly important groups of bacteria in the gut that can coexist with other bacteria across a range of conditions. Conclusions IBD patients exhibited a less diverse gut microbiome compared to healthy individuals. Bacterial groups which changed in IBD patients were found to be groups which do not co-exist well with common commensal gut bacteria, whereas bacterial groups which did not change in patients with IBD were found to commonly co-exist with commensal gut microbiota. This gives a potential insight into the dynamics of the gut microbiota in patients with IBD.

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