Diurnal Timing Dependent Alterations in Gut Microbial Composition Are Synchronously Linked to Salt-Sensitive Hypertension and Renal Damage

Alterations of diurnal rhythms of blood pressure (BP) and reshaping of gut microbiota are both independently associated with hypertension. However, the relationships between biorhythms of BP and gut microbial composition are unknown. We hypothesized that diurnal timing-associated alterations of microbial compositions are synchronous with diurnal rhythmicity, dip in BP, and renal function. To test this hypothesis, Dahl salt-sensitive (S) rats on low- and high-salt diets were examined for time of day effects on gut microbiota, BP, and indicators of renal damage. Major shifts in night and day patterns of specific groups of microbiota were observed between the dark (active) and light (rest) phases, which correlated with diurnal rhythmicity of BP. The diurnal abundance of Firmicutes, Bacteroidetes, and Actinobacteria were independently associated with BP. Discrete bacterial taxa were observed to correlate independently or interactively with one or more of the following 3 factors: (1) BP rhythm, (2) dietary salt, and (3) dip in BP. Phylogenetic Investigation of Communities revealed diurnal timing effects on microbial pathways, characterized by upregulated biosynthetic processes during the active phase of host, and upregulated degradation pathways of metabolites in the resting phase. Additional metagenomics functional pathways with rhythm variations were noted for aromatic amino acid metabolism and taurine metabolism. These diurnal timing dependent changes in microbiota, their functional pathways, and BP dip were associated with concerted effects of the levels of renal lipocalin 2 and kidney injury molecule-1 expression. These data provide evidence for a firm and concerted diurnal timing effects of BP, renal damage, and select microbial communities.

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

The ISME Journal ◽

10.1038/s41396-021-00998-8 ◽

2021 ◽

Author(s):

Yueqiong Ni ◽

Zoltan Lohinai ◽

Yoshitaro Heshiki ◽

Balazs Dome ◽

Judit Moldvay ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Cancer Patients ◽

Gut Microbiome ◽

Human Gut ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Lung Cancer Patients ◽

Microbial Species ◽

Functional Pathways

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

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Distinct gut microbial communities and metabolic functions are associated with cachexia in lung cancer patients

10.21203/rs.3.rs-30539/v1 ◽

2020 ◽

Author(s):

Yueqiong Ni ◽

Zoltan Lohinai ◽

Yoshitaro Heshiki ◽

Balazs Dome ◽

Judit Moldvay ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Cancer Patients ◽

Clinical Setting ◽

Gut Microbiome ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Lung Cancer Patients ◽

Microbial Species ◽

Functional Pathways

Abstract Background Cachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in the clinical setting by integrating shotgun metagenomics and plasma metabolomics of 38 lung cancer patients, with known cachexia status. Results The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, as well as vitamins, were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of plasma BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with the gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in the cancer cachectic patients. The involvement of gut microbiome in cachexia was further observed in a high-performance machine learning model that uses solely gut microbial taxonomic and pathway features to differentiate cachectic from non-cachectic cancer patients. Conclusions Our study demonstrates the links between host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible future therapeutic applications.

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Abstract P150: Concerted Diurnal Rhythms Of Gut Microbiota With Salt-sensitive Hypertension And Renal Damage

Hypertension ◽

10.1161/hyp.76.suppl_1.p150 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Juthika Mandal ◽

Saroj Chakraborty ◽

Xi Cheng ◽

Sarah Galla ◽

Anay Hindupur ◽

...

Keyword(s):

Blood Pressure ◽

Gut Microbiota ◽

Diurnal Rhythm ◽

Active Phase ◽

High Salt ◽

Diurnal Rhythms ◽

Physiological Feature ◽

Low Salt ◽

Salt Sensitive Hypertension ◽

Diurnal Rhythmicity

Circadian, diurnal rhythm is a vital physiological feature of life forms, which enables holobionts to adapt to the day and night cycles. Evidence suggests that both factions of the holobiont, i.e, the host and its microbiota demonstrate physiological circadian rhythms. Blood pressure is a good example of a host physiological feature with a well-defined diurnal rhythm. In a healthy human, blood pressure (BP) rises to its peak during awakening morning hours and declines to the lowest level during night. In salt-sensitive hypertension, aberrant diurnal rhythms of BP and gut dysbiosis have been demonstrated. Given the critical role of gut microbiota in BP regulation, our current objective was to investigate whether there are synchronous rhythms of holobiont in rodents on low salt and high salt diets and if inflammation pattern also changes diurnally. We examined Dahl Salt-Sensitive (S) rats on low (0.3%) and high (2%) salt diets and BP and inflammation pattern was checked. As hypothesized, both microbiota and kidney inflammation showed diurnal rhythm in response to low salt and high salt diet. Major shifts in diurnal patterns of specific groups of microbiota were observed between the dark (active) and light (rest) phases, which correlated with the diurnal rhythmicity of BP. Diurnal rhythms of Firmicutes, Bacteroidetes and Actinobacteria were independently associated with BP. Discrete bacterial taxa were observed to correlate independently or interactively with one or more of the following 3 factors- 1) BP rhythm, 2) dietary salt, 3) amplitude of BP. PICRUSt analysis revealed diurnal rhythmicity of microbial pathways, characterized by microbiota upregulated biosynthetic processes during active phase and upregulated degradation pathways of metabolites in resting phase. These diurnal changes in microbiota, their functional pathways and BP amplitude were associated with concerted rhythmicity of renal Lipocalin 2 and Kim1 expression and circulating β-hydroxybutyrate in high salt S rats. Such concerted rhythmicity of holobiont with peak of changes at active phase of salt hypertension suggests that targeting this timepoint to reshape microbiota and/or intervene with medication could efficiently benefit the hypertensives

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Diversity, Composition and Functional Inference of Gut Microbiota in Indian Cabbage white Pieris canidia (Lepidoptera: Pieridae)

Life ◽

10.3390/life10110254 ◽

2020 ◽

Vol 10 (11) ◽

pp. 254

Author(s):

Ying Wang ◽

Jianqing Zhu ◽

Jie Fang ◽

Li Shen ◽

Shuojia Ma ◽

...

Keyword(s):

Gut Microbiota ◽

16S Rrna Gene Sequencing ◽

Adult Survival ◽

Rrna Gene ◽

Life Stages ◽

Microbial Composition ◽

Significant Difference ◽

Functional Inference ◽

Rrna Gene Sequencing ◽

Insect Fitness

We characterized the gut microbial composition and relative abundance of gut bacteria in the larvae and adults of Pieris canidia by 16S rRNA gene sequencing. The gut microbiota structure was similar across the life stages and sexes. The comparative functional analysis on P. canidia bacterial communities with PICRUSt showed the enrichment of several pathways including those for energy metabolism, immune system, digestive system, xenobiotics biodegradation, transport, cell growth and death. The parameters often used as a proxy of insect fitness (development time, pupation rate, emergence rate, adult survival rate and weight of 5th instars larvae) showed a significant difference between treatment group and untreated group and point to potential fitness advantages with the gut microbiomes in P. canidia. These data provide an overall view of the bacterial community across the life stages and sexes in P. canidia.

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Monitoring the variation in the gut microbiota of captive woolly monkeys related to changes in diet during a reintroduction process

Scientific Reports ◽

10.1038/s41598-021-85990-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Camilo Quiroga-González ◽

Luis Alberto Chica Cardenas ◽

Mónica Ramírez ◽

Alejandro Reyes ◽

Camila González ◽

...

Keyword(s):

Gut Microbiota ◽

Site Conditions ◽

Microbiota Composition ◽

Microbial Composition ◽

Bacterial Composition ◽

Diet Diversity ◽

Woolly Monkeys ◽

The Moment ◽

Positive Effect ◽

Lagothrix Lagothricha

AbstractMicrobiome is known to play an important role in the health of organisms and different factors such as diet have been associated with modifications in microbial communities. Differences in the microbiota composition of wild and captive animals has been evaluated; however, variation during a reintroduction process in primates has never been reported. Our aim was to identify changes in the bacterial composition of three individuals of reintroduced woolly monkeys (Lagothrix lagothricha) and the variables associated with such changes. Fecal samples were collected and the V4 region of the 16S rRNA gene was sequenced to determine gut microbial composition and functionality. Individual samples from released individuals showed a higher microbial diversity after being released compared to before liberation, associated with changes in their diet. Beta diversity and functionality analysis showed separation of samples from released and captive conditions and the major factor of variation was the moment of liberation. This study shows that intestinal microbiota varies depending on site conditions and is mainly associated with diet diversity. The intake of food from wild origin by released primates may promote a positive effect on gut microbiota, improving health, and potentially increasing success in reintroduction processes.

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

Life ◽

10.3390/life11030246 ◽

2021 ◽

Vol 11 (3) ◽

pp. 246

Author(s):

Felix C.F. Schmitt ◽

Martin Schneider ◽

William Mathejczyk ◽

Markus A. Weigand ◽

Jane C. Figueiredo ◽

...

Keyword(s):

Colorectal Cancer ◽

Postoperative Complications ◽

Gut Microbiota ◽

Gut Microbiome ◽

Tumor Resection ◽

Microbial Composition ◽

Colorectal Cancer Surgery ◽

Long Term Changes ◽

Stool Samples

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

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Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis

Scientific Reports ◽

10.1038/s41598-021-87973-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lena Öhman ◽

Anders Lasson ◽

Anna Strömbeck ◽

Stefan Isaksson ◽

Marcus Hesselmar ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Disease Activity ◽

Temporal Dynamics ◽

Fecal Microbiota ◽

Disease Stage ◽

Dietary Interventions ◽

Microbial Composition ◽

Fecal Samples ◽

Specific Species

AbstractPatients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2–6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3–10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

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The Influence of Gut Microbiota on the Cardiovascular System Under Conditions of Obesity and Chronic Stress

Current Hypertension Reports ◽

10.1007/s11906-021-01144-7 ◽

2021 ◽

Vol 23 (5) ◽

Author(s):

Piotr Dubinski ◽

Katarzyna Czarzasta ◽

Agnieszka Cudnoch-Jedrzejewska

Keyword(s):

Gut Microbiota ◽

Cardiovascular System ◽

Chronic Stress ◽

Human Body ◽

High Fat Diet ◽

Intestinal Barrier ◽

Microbial Composition ◽

Enhanced Absorption ◽

Bacterial Accumulation ◽

Metabolic Endotoxemia

Abstract Purpose of Review Based on the available data, it can be assumed that microbiota is an integral part of the human body. The most heavily colonized area of the human body is the gut, with bacterial accumulation ranging from 101–103 cells/g in the upper intestine to 1011–1012 cells/g in the colon. However, colonization of the gut is not the same throughout, as it was shown that there are differences between the composition of the microbiota in the intestine lumen and in the proximity of the mucus layer. Recent Findings Gut microbiota gradient can be differentially regulated by factors such as obesity and chronic stress. In particular, a high fat diet influences the gut microbial composition. It was also found that chronic stress may cause the development of obesity and thus change the organization of the intestinal barrier. Recent research has shown the significant effect of intestinal microflora on cardiovascular function. Enhanced absorption of bacterial fragments, such as lipopolysaccharide (LPS), promotes the onset of “metabolic endotoxemia,” which could activate toll-like receptors, which mediates an inflammatory response and in severe cases could cause cardiovascular diseases. It is presumed that the intestinal microbiota, and especially its metabolites (LPS and trimethylamine N-oxide (TMAO)), may play an important role in the pathogenesis of arterial hypertension, atherosclerosis, and heart failure. Summary This review focuses on how gut microbiota can change the morphological and functional activity of the cardiovascular system in the course of obesity and in conditions of chronic stress.

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

European Heart Journal ◽

10.1093/ehjci/ehaa946.3823 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Roessler ◽

F Zimmermann ◽

D Schmidt ◽

U Escher ◽

A Jasina ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Gut Microbiome ◽

Interindividual Variation ◽

Funding Source ◽

Microbial Composition ◽

Atorvastatin Treatment ◽

Qrt Pcr ◽

16S Rna ◽

Regulatory Properties

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

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The Effects of Genetic Relatedness on the Preterm Infant Gut Microbiota

Microorganisms ◽

10.3390/microorganisms9020278 ◽

2021 ◽

Vol 9 (2) ◽

pp. 278

Author(s):

Shen Jean Lim ◽

Miriam Aguilar-Lopez ◽

Christine Wetzel ◽

Samia V. O. Dutra ◽

Vanessa Bray ◽

...

Keyword(s):

Gut Microbiota ◽

Preterm Infant ◽

Neonatal Intensive Care ◽

Genetic Relatedness ◽

Bovine Milk ◽

Alpha Diversity ◽

Neonatal Intensive Care Units ◽

Rrna Gene ◽

Microbial Composition ◽

Operational Taxonomic Units

The preterm infant gut microbiota is influenced by environmental, endogenous, maternal, and genetic factors. Although siblings share similar gut microbial composition, it is not known how genetic relatedness affects alpha diversity and specific taxa abundances in preterm infants. We analyzed the 16S rRNA gene content of stool samples, ≤ and >3 weeks postnatal age, and clinical data from preterm multiplets and singletons at two Neonatal Intensive Care Units (NICUs), Tampa General Hospital (TGH; FL, USA) and Carle Hospital (IL, USA). Weeks on bovine milk-based fortifier (BMF) and weight gain velocity were significant predictors of alpha diversity. Alpha diversity between siblings were significantly correlated, particularly at ≤3 weeks postnatal age and in the TGH NICU, after controlling for clinical factors. Siblings shared higher gut microbial composition similarity compared to unrelated individuals. After residualizing against clinical covariates, 30 common operational taxonomic units were correlated between siblings across time points. These belonged to the bacterial classes Actinobacteria, Bacilli, Bacteroidia, Clostridia, Erysipelotrichia, and Negativicutes. Besides the influence of BMF and weight variables on the gut microbial diversity, our study identified gut microbial similarities between siblings that suggest genetic or shared maternal and environmental effects on the preterm infant gut microbiota.

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