Abstract MP28: A New Gut Microbial Metabolite Derived From Low Fibre Intake

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Chudan Xu ◽  
Michael Nakai ◽  
Rikeish Muralitharan ◽  
Evany Dinakis ◽  
Hamdi Jama ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Fold Change ◽  
Rrna Gene ◽  
Microbial Metabolite ◽  
Fibre Intake ◽  
High Fibre

Low fermentable fibre intake has emerged as an important risk factor for hypertension through changes in the gut microbiota, but the biological pathways and specific metabolites involved are unknown. We performed untargeted liquid-chromatography mass spectrometry metabolomic profiling on plasma samples from 16 mice fed low or high fibre diets and 70 participants with ambulatory blood pressure recordings. Mouse gut microbiome was analysed using 16S rRNA gene sequencing . In vitro experiments were performed in human peripheral blood mononuclear cells (PBMCs) to assess the role of a new metabolite in inflammatory responses. The phenylalanine, tyrosine and tryptophan biosynthesis pathway was upregulated in hypertensive compared to normotensive participants, as well as in low compared to high fibre fed mice (both q <0.05, pathway impact factor=1.0). In particular, p-cresol glucuronide (pCG), an end-product of tyrosine metabolism, was higher in mice fed with low compared to high fibre in both angiotensin II-treated ( q =4.83 x10 -4 , fold change= 88) and sham groups ( q =1.56 x10 -4 , fold change= 297). pCG is derived from p-Cresol, which is produced by the gut microbiota. β-diversity analyses showed that distinct gut microbiome compositions were associated with levels of pCG in plasma (q<0.05). While diet had a major effect on the gut microbiome (~30%), we found that pCG levels were associated with 5.7-6.3% of the total gut microbiome variation. This is relevant as pCG’s precursor, p-cresol, may inhibit the growth of certain types of bacteria. To understand the possible role of pCG in hypertension, human PBMCs obtained commercially were treated with physiological levels of pCG for 24 hours. This resulted in an increase in proinflammatory IL-17A mRNA ( P =0.01, fold change= 1.79) and a decrease in anti-inflammatory IL-10 mRNA ( P =0.014, fold change= -2.32) when compared to untreated and mock-treated cells. In conclusion, tyrosine biotransformation was associated with both human hypertension and low fibre intake. pCG, a key microbial metabolite derived from the metabolism of tyrosine, was associated with distinct gut microbiome compositions and modulated inflammatory response, suggesting it may be involved in the genesis of hypertension.

scholarly journals The Impact of Anthelmintic Treatment on Human Gut Microbiota Based on Cross-Sectional and Pre- and Postdeworming Comparisons in Western Kenya

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Alice V. Easton ◽  
Mariam Quiñones ◽  
Ivan Vujkovic-Cvijin ◽  
Rita G. Oliveira ◽  
Stella Kepha ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Parasites ◽  
Fold Change ◽  
Rrna Gene ◽  
Human Gut ◽  
Microbial Composition ◽  
Content Type ◽  
Average Fold Change ◽  
The Impact

ABSTRACT Murine studies suggest that the presence of some species of intestinal helminths is associated with changes in host microbiota composition and diversity. However, studies in humans have produced varied conclusions, and the impact appears to vary widely depending on the helminth species present. To demonstrate how molecular approaches to the human gut microbiome can provide insights into the complex interplay among disparate organisms, DNA was extracted from cryopreserved stools collected from residents of 5 rural Kenyan villages prior to and 3 weeks and 3 months following albendazole (ALB) therapy. Samples were analyzed by quantitative PCR (qPCR) for the presence of 8 species of intestinal parasites and by MiSeq 16S rRNA gene sequencing. Based on pretreatment results, the presence of neither Ascaris lumbricoides nor Necator americanus infection significantly altered the overall diversity of the microbiota in comparison with age-matched controls. Following ALB therapy and clearance of soil-transmitted helminths (STH), there were significant increases in the proportion of the microbiota made up by Clostridiales (P = 0.0002; average fold change, 0.57) and reductions in the proportion made up by Enterobacteriales (P = 0.0004; average fold change, −0.58). There was a significant posttreatment decrease in Chao1 richness, even among individuals who were uninfected pretreatment, suggesting that antimicrobial effects must be considered in any posttreatment setting. Nevertheless, the helminth-associated changes in Clostridiales and Enterobacteriales suggest that clearance of STH, and of N. americanus in particular, alters the gut microbiota. IMPORTANCE The gut microbiome is an important factor in human health. It is affected by what we eat, what medicines we take, and what infections we acquire. In turn, it affects the way we absorb nutrients and whether we have excessive intestinal inflammation. Intestinal worms may have an important impact on the composition of the gut microbiome. Without a complete understanding of the impact of mass deworming programs on the microbiome, it is impossible to accurately calculate the cost-effectiveness of such public health interventions and to guard against any possible deleterious side effects. Our research examines this question in a “real-world” setting, using a longitudinal cohort, in which individuals with and without worm infections are treated with deworming medication and followed up at both three weeks and three months posttreatment. We quantify the impact of roundworms and hookworms on gut microbial composition, suggesting that the impact is small, but that treatment of hookworm infection results in significant changes. This work points to the need for follow-up studies to further examine the impact of hookworm on the gut microbiota and determine the health consequences of the observed changes.

scholarly journals Alterations of the Gut Microbiome and Metabolome in Patients With Proliferative Diabetic Retinopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Panpan Ye ◽  
Xueyou Zhang ◽  
Yufeng Xu ◽  
Jia Xu ◽  
Xiaoxiao Song ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Gut Microbiota ◽  
Proliferative Diabetic Retinopathy ◽  
Gut Microbiome ◽  
16S Rrna Gene Sequencing ◽  
Diabetic Patients ◽  
Rrna Gene ◽  
Bacterial Composition ◽  
Rrna Gene Sequencing

Diabetic retinopathy (DR) has been reported to associate with gut microbiota alterations in murine models and thus “gut-retina-axis” has been proposed. However, the role of gut microbiome and the associated metabolism in DR patients still need to be elucidated. In this study, we collected fecal samples from 45 patients with proliferative diabetic retinopathy (PDR) and 90 matched diabetic patients (1:2 according to age, sex, and duration of diabetes) without DR (NDR) and performed 16S rRNA gene sequencing and untargeted metabolomics. We observed significantly lower bacterial diversity in the PDR group than that in the NDR group. Differential gut bacterial composition was also found, with significant depletion of 22 families (e.g., Coriobacteriaceae, Veillonellaceae, and Streptococcaceae) and enrichment of two families (Burkholderiaceae and Burkholderiales_unclassified) in the PDR group as compared with the NDR group. There were significantly different fecal metabolic features, which were enriched in metabolic pathways such as arachidonic acid and microbial metabolism, between the two groups. Among 36 coabundance metabolite clusters, 11 were positively/negatively contributed to PDR using logistic regression analysis. Fifteen gut microbial families were significantly correlated with the 11 metabolite clusters. Furthermore, a fecal metabolite-based classifier was constructed to distinguish PDR patients from NDR patients accurately. In conclusion, PDR is associated with reduced diversity and altered composition of gut microbiota and specific microbe-metabolite interplay. Our findings help to better understand the disease pathogenesis and provide novel diagnostic and therapeutic targets for PDR.

scholarly journals Alterations of the Gut Microbiome and Metabolome in Patients with Proliferative Diabetic Retinopathy

2020 ◽  
Author(s):  
Ke Yao ◽  
Panpan Ye ◽  
Xueyou Zhang ◽  
Yufeng Xu ◽  
Jia Xu ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
16S Rrna Gene Sequencing ◽  
Diabetic Patients ◽  
Rrna Gene ◽  
Bacterial Composition ◽  
Diagnostic Biomarkers ◽  
Rrna Gene Sequencing

Abstract Background: Diabetic retinopathy (DR) has been reported to associate with gut microbiota alterations in murine models and thus “gut-retina-axis” has been proposed. However, the role of gut microbiome and the associated metabolism in DR patients still need to be elucidated. Results: Fecal samples from 45 patients with proliferative DR (PDR) and 90 matched diabetic patients (1:2 according to age, sex and duration of diabetes) without DR (NDR) were subjected to 16S rRNA gene sequencing and untargeted metabolomics. Significantly lower bacterial diversity was observed in PDR group than that in NDR group. Differential gut bacterial composition was found, with significant depletion of 22 families (e.g., Coriobacteriaceae, Veillonellaceae and Streptococcaceae) and enrichment of 2 families (Burkholderiaceae and Burkholderiales_unclassified) in PDR group as compared to NDR group. There were significantly different fecal metabolic features, which were enriched in metabolic pathways such as arachidonic acid and microbial metabolism, between the two groups. Among 36 co-abundance metabolite clusters, 11 were positively/negatively contributed to PDR using logistic regression analysis. Fifteen gut microbial families were significantly correlated with the 11 metabolite clusters. Furthermore, a fecal metabolites-based classifier was constructed to distinguish PDR patients from NDR patients accurately.Conclusions: PDR is associated with reduced diversity and altered composition of gut microbiota and specific microbe-metabolite interplay. Our findings help to better understand the disease pathogenesis and provide novel diagnostic biomarkers and therapeutic targets for PDR.

scholarly journals Gut Microbiome in a Russian Cohort of Pre- and Post-Cholecystectomy Female Patients

2021 ◽  
Vol 11 (4) ◽  
pp. 294
Author(s):  
Irina Grigor’eva ◽  
Tatiana Romanova ◽  
Natalia Naumova ◽  
Tatiana Alikina ◽  
Alexey Kuznetsov ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Gallstone Disease ◽  
Illumina Miseq ◽  
Rrna Gene ◽  
Bacterial Phyla ◽  
Female Patients ◽  
Composition And Structure ◽  
Before And After

The last decade saw extensive studies of the human gut microbiome and its relationship to specific diseases, including gallstone disease (GSD). The information about the gut microbiome in GSD-afflicted Russian patients is scarce, despite the increasing GSD incidence worldwide. Although the gut microbiota was described in some GSD cohorts, little is known regarding the gut microbiome before and after cholecystectomy (CCE). By using Illumina MiSeq sequencing of 16S rRNA gene amplicons, we inventoried the fecal bacteriobiome composition and structure in GSD-afflicted females, seeking to reveal associations with age, BMI and some blood biochemistry. Overall, 11 bacterial phyla were identified, containing 916 operational taxonomic units (OTUs). The fecal bacteriobiome was dominated by Firmicutes (66% relative abundance), followed by Bacteroidetes (19%), Actinobacteria (8%) and Proteobacteria (4%) phyla. Most (97%) of the OTUs were minor or rare species with ≤1% relative abundance. Prevotella and Enterocossus were linked to blood bilirubin. Some taxa had differential pre- and post-CCE abundance, despite the very short time (1–3 days) elapsed after CCE. The detailed description of the bacteriobiome in pre-CCE female patients suggests bacterial foci for further research to elucidate the gut microbiota and GSD relationship and has potentially important biological and medical implications regarding gut bacteria involvement in the increased GSD incidence rate in females.

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.

scholarly journals Guild-based analysis for understanding gut microbiome in human health and diseases

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Guojun Wu ◽  
Naisi Zhao ◽  
Chenhong Zhang ◽  
Yan Y. Lam ◽  
Liping Zhao
Keyword(s):  
Gut Microbiota ◽  
Human Health ◽  
Gut Microbiome ◽  
Association Studies ◽  
Causative Role ◽  
Disease Phenotypes ◽  
Genetic Complexity ◽  
Causative Agents ◽  
Specific Health

AbstractTo demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem’s higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same “guild” if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of “guild” to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases.

scholarly journals Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shenhai Gong ◽  
Yinglin Feng ◽  
Yunong Zeng ◽  
Huanrui Zhang ◽  
Meiping Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
16S Rrna ◽  
Gut Microbiota ◽  
Gene Sequencing ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Metabolomic Analysis ◽  
Rrna Gene Sequencing ◽  
And Oxidative Stress

Abstract Background Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown. Methods We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment. Results 16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity. Conclusions This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.

scholarly journals Role of lung and gut microbiota on lung cancer pathogenesis

2021 ◽  
Author(s):  
Yue Zhao ◽  
Yuxia Liu ◽  
Shuang Li ◽  
Zhaoyun Peng ◽  
Xiantao Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Cancer Progression ◽  
Gut Microbiome ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Cancer Pathogenesis ◽  
Research Findings ◽  
Relationship Of

Abstract Background Lung cancer is the leading cause of cancer-related deaths worldwide (Ferlay et al., Int J Cancer 136:E359–386, 2015). In addition, lung cancer is associated with the highest mortality among all cancer types (Wu et al., Exp Ther Med 16:3004–3010, 2018). Previous studies report that microbiota play an important role in lung cancer. Notably, changes in lung and gut microbiota, are associated with progression of lung cancer. Several studies report that lung and gut microbiome promote lung cancer initiation and development by modulating metabolic pathways, inhibiting the function of immune cells, and producing pro-inflammatory factors. In addition, some factors such as microbiota dysbiosis, affect production of bacteriotoxins, genotoxicity and virulence effect, therefore, they play a key role in cancer progression. These findings imply that lung and gut microbiome are potential markers and targets for lung cancer. However, the role of microbiota in development and progression of lung cancer has not been fully explored. Purpose The aim of this study was to systemically review recent research findings on relationship of lung and gut microbiota with lung cancer. In addition, we explored gut–lung axis and potential mechanisms of lung and gut microbiota in modulating lung cancer progression. Conclusion Pulmonary and intestinal flora influence the occurrence, development, treatment and prognosis of lung cancer, and will provide novel strategies for prevention, diagnosis, and treatment of lung cancer.

scholarly journals Gut Microbiome Changes in Captive Plateau Zokors (Eospalax baileyi)

2021 ◽  
Vol 17 ◽  
pp. 117693432199635
Author(s):  
Daoxin Liu ◽  
Pengfei Song ◽  
Jingyan Yan ◽  
Haijing Wang ◽  
Zhenyuan Cai ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
High Throughput Sequencing ◽  
Tibet Plateau ◽  
Rrna Gene ◽  
Diversity Analysis ◽  
Bacterial Phyla ◽  
In Captivity ◽  
Relative Abundances ◽  
Plateau Zokor

Wild-caught animals must cope with drastic lifestyle and dietary changes after being induced to captivity. How the gut microbiome structure of these animals will change in response receives increasing attention. The plateau zokor ( Eospalax baileyi), a typic subterranean rodent endemic to the Qinghai-Tibet plateau, spends almost the whole life underground and is well adapted to the environmental pressures of both plateau and underground. However, how the gut microbiome of the plateau zokor will change in response to captivity has not been reported to date. This study compared the microbial community structure and functions of 22 plateau zokors before (the WS group) and after being kept in captivity for 15 days (the LS group, fed on carrots) using the 16S rRNA gene via high-throughput sequencing technology. The results showed that the LS group retained 973 of the 977 operational taxonomic units (OTUs) in the WS group, and no new OTUs were found in the LS group. The dominant bacterial phyla were Bacteroides and Firmicutes in both groups. In alpha diversity analysis, the Shannon, Sobs, and ACE indexes of the LS group were significantly lower than those of the WS group. A remarkable difference ( P < 0.01) between groups was also detected in beta diversity analysis. The UPGMA clustering, NMDS, PCoA, and Anosim results all showed that the intergroup difference was significantly greater than the intragroup difference. And compared with the WS group, the intragroup difference of the gut microbiota in the LS group was much larger, which failed to support the assumption that similar diets should drive convergence of gut microbial communities. PICRUSt revealed that although some functional categories displayed significant differences between groups, the relative abundances of these categories were very close in both groups. Based on all the results, we conclude that as plateau zokors enter captivity for a short time, although the relative abundances of different gut microbiota categories shifted significantly, they can maintain almost all the OTUs and the functions of the gut microbiota in the wild. So, the use of wild-caught plateau zokors in gut microbial studies is acceptable if the time in captivity is short.

scholarly journals Nanopore-Sequencing Characterization of the Gut Microbiota of Melolontha melolontha Larvae: Contribution to Protection against Entomopathogenic Nematodes?

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 396
Author(s):  
Ewa Sajnaga ◽  
Marcin Skowronek ◽  
Agnieszka Kalwasińska ◽  
Waldemar Kazimierczak ◽  
Karolina Ferenc ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Entomopathogenic Nematodes ◽  
Bacterial Species ◽  
Antagonistic Activity ◽  
Rrna Gene ◽  
Nanopore Sequencing ◽  
Bacterial Phyla ◽  
Melolontha Melolontha

This study focused on the potential relationships between midgut microbiota of the common cockchafer Melolontha melolontha larvae and their resistance to entomopathogenic nematodes (EPN) infection. We investigated the bacterial community associated with control and unsusceptible EPN-exposed insects through nanopore sequencing of the 16S rRNA gene. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were the most abundant bacterial phyla within the complex and variable midgut microbiota of the wild M. melolontha larvae. The core microbiota was found to include 82 genera, which accounted for 3.4% of the total number of identified genera. The EPN-resistant larvae differed significantly from the control ones in the abundance of many genera belonging to the Actinomycetales, Rhizobiales, and Clostridiales orders. Additionally, the analysis of the microbiome networks revealed different sets of keystone midgut bacterial genera between these two groups of insects, indicating differences in the mutual interactions between bacteria. Finally, we detected Xenorhabdus and Photorhabdus as gut residents and various bacterial species exhibiting antagonistic activity against these entomopathogens. This study paves the way to further research aimed at unravelling the role of the host gut microbiota on the output of EPN infection, which may contribute to enhancement of the efficiency of nematodes used in eco-friendly pest management.

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