scholarly journals Higher Trimethylamine- N -Oxide Plasma Levels with Increasing Age Are Mediated by Diet and Trimethylamine-Forming Bacteria

mSystems ◽  
2021 ◽  
Author(s):  
Silke Rath ◽  
Katharina Rox ◽  
Sven Kleine Bardenhorst ◽  
Ulf Schminke ◽  
Marcus Dörr ◽  
...  

Many cohort studies have investigated the link between diet and plasma TMAO levels, reporting incongruent results, while gut microbiota were only recently included into analyses. In these studies, taxonomic data were recorded that are not a good proxy for TMA formation, as specific members of various taxa exhibit genes catalyzing this reaction, demanding function-based technologies for accurate quantification of TMA-synthesizing bacteria.

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1426
Author(s):  
Mauro Lombardo ◽  
Giovanni Aulisa ◽  
Daniele Marcon ◽  
Gianluca Rizzo ◽  
Maria Grazia Tarsisano ◽  
...  

Introduction: Trimethylamine N-oxide (TMAO) may play a key mediator role in the relationship between the diet, gut microbiota and cardiovascular diseases, particularly in people with kidney failure. The aim of this review is to evaluate which foods have a greater influence on blood or urinary trimethylamine N-oxide (TMAO) levels. Methods: 391 language articles were screened, and 27 were analysed and summarized for this review, using the keywords “TMAO” AND “egg” OR “meat” OR “fish” OR “dairy” OR “vegetables” OR “fruit” OR “food” in December 2020. Results: A strong correlation between TMAO and fish consumption, mainly saltwater fish and shellfish, but not freshwater fish, has been demonstrated. Associations of the consumption of eggs, dairy and meat with TMAO are less clear and may depend on other factors such as microbiota or cooking methods. Plant-based foods do not seem to influence TMAO but have been less investigated. Discussion: Consumption of saltwater fish, dark meat fish and shellfish seems to be associated with an increase in urine or plasma TMAO values. Further studies are needed to understand the relationship between increased risk of cardiovascular disease and plasma levels of TMAO due to fish consumption. Interventions coupled with long-term dietary patterns targeting the gut microbiota seem promising.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Mieke Steenbeke ◽  
Sophie Valkenburg ◽  
Wim Van Biesen ◽  
Joris Delanghe ◽  
Marijn Speeckaert ◽  
...  

Abstract Background and Aims Chronic kidney disease (CKD) is characterized by gut dysbiosis. We recently demonstrated a decrease of short-chain fatty acid (SCFA) producing bacterial species with the progression of CKD. Besides, levels of protein-bound uremic toxins (PBUTs) and post-translational modifications of protein are increased in CKD, both are risk factors for accelerated cardiovascular morbidity and mortality. The link between the gut-kidney axis and protein carbamylation is unclear. The aim of the study was to explore the relation between carbamylated albumin, estimated by the albumin symmetry factor, and plasma levels of PBUTs, fecal levels of SCFAs (ongoing), and the abundance of related gut microbiota in different stages of CKD (1-5). Method The study cohort includes 103 non-dialyzed CKD patients (stages 1-5). Serum proteins were detected by capillary electrophoresis and UV absorbance at 214 nm with the symmetry factor as a marker of albumin carbamylation [the lower the symmetry factor, the more carbamylated albumin]. The quantification of PBUTs and SCFAs in plasma and fecal samples, respectively, using validated UPLC methods. Results The Pearson correlation coefficient (r) shows a positive correlation between the albumin symmetry factor and the estimated glomerular filtration rate (eGFR) (r=0.3025; p=0.0019). The albumin symmetry factor correlates positively with the abundance of Butyricicoccus spp. (r= 0.3211; p=0.0009), Faecalibacterium prausnitzii (r=0.2765; p=0.0047) and Roseburia spp. (r=0.2527; p=0.0100) and negatively with the PBUTs, p-cresyl sulfate (pCS) (r=-0.2819; p=0.0039), p-cresyl glucuronide (pCG) (r=-0.2819; p=0.0039) and indoxyl sulfate (IxS) (r=-0.2650; p=0.0068). Conclusion The decreased abundance of SCFA producing gut bacteria with the progression of CKD can evoke unfavorable conditions in the gut. This can contribute to increased plasma levels of PBUTs potentially (indirectly) playing a role in albumin carbamylation. It will be further explored whether fecal levels of SCFAs are affected in parallel and could be potential targets to restore gut dysbiosis and uremia.


2006 ◽  
Vol 86 (4) ◽  
pp. 511-522 ◽  
Author(s):  
H. Namkung ◽  
J. Gong ◽  
H. Yu ◽  
C. F. M. de Lange

The effect of feeding pharmacological levels of zinc (Zn) and copper (Cu) to newly weaned piglets on growth performance, circulating cytokines levels and gut microbiota was investigated. One hundred eighty piglets [5.90 ± 0.18 kg body weight (BW); six pigs per pen] weaned at 16 to 19 d of age were fed diets containing 3000 ppm additional Zn, 250 ppm additional Cu or a control diet (150 ppm Zn, 15 ppm Cu) for 14 d post-weaning (weeks 1 and 2). Pigs were fed a control diet for an additional 2 wk. Pigs were injected intramuscularly on days 13 and 19 with either 75 μg kg-1 BW of coliform lipopolysaccharide (LPS) or an equivalent amount of saline. Blood samples were collected 3 h after LPS injection to measure plasma levels of cytokines and cortisol. Digesta of ileum and colon were collected from non-challenged pigs on days 14 and 28 to evaluate microbiota using conventional culturing methods and polymerase chain reaction and denaturing gradient gel electrophoresis (PCRDGGE) analysis of the 16S rRNA genes. There were no interactive effects of diet and LPS challenge on growth performance (P > 0.10). Compared with the control, high dietary Zn and Cu increased (P < 0.01) average daily gain (ADG) during weeks 1 (0.125, 0.091 vs. 0.074 kg; P < 0.05) and 2 (0.240, 0.270 vs. 0.155 kg; P < 0.01) only. LPS injection reduced ADG during weeks 2 and 4 (P < 0.01). Dietary treatment did not affect feed efficiency (P > 0.10). Challenging pigs with LPS reduced (P < 0.01) feed efficiency during week 2, but increased (P < 0.05) feed efficiency during week 3. There were no interactive effects between diet and LPS on plasma cytokines levels, except for cortisol (P < 0.05). Plasma levels of cytokines (interleukin-1β, interferon-γ, tumour necrosis factor-α) and cortisol increased (P < 0.01) in pigs challenged with LPS. The high levels of dietary Zn and Cu reduced (P < 0.05) the increases in plasma cortisol level in LPS-challenged pigs at days 9 and 19. There were no differences among the dietary treatments in counts of coliforms and lactobacillus in the digesta from ileum and colon (P > 0.10). PCR-DGGE analysis showed that high levels of dietary Zn and particularly Cu significantly reduced the diversity of ileal microbiota. The effect on microbiota diversity was reversible when dietary Zn and Cu were removed. Enhanced growth performance of the newly weaned piglets fed high dietary Zn and Cu appears mediated via changes in gut microbiota as well as a reduced cortisol response following an immune challenge. Key words: Piglets, zinc, copper, lipopolysaccharide, gut microbiota, cytokines


2021 ◽  
Vol 8 ◽  
Author(s):  
Jiali Chen ◽  
Fuchang Li ◽  
Weiren Yang ◽  
Shuzhen Jiang ◽  
Yang Li

The experiment was conducted to compare the differences of gut microbiota and metabolic status of sows with different litter sizes on days 30 and 110 of gestation, and uncover the relationship between the composition of maternal gut microbiota during gestation and sow reproductive performance. Twenty-six Large White × Landrace crossbred multiparous sows (2nd parity) with similar back fat thickness and body weight were assigned to two groups [high-reproductive performance group (HP group) and low-reproductive performance group (LP group)] according to their litter sizes and fed a common gestation diet. Results showed that compared with LP sows, HP sows had significantly lower plasma levels of triglyceride (TG) on gestation d 30 (P &lt; 0.05), but had significantly higher plasma levels of TG, non-esterified fatty acid, tumor necrosis factor-α, and immunoglobulin M on gestation d 110 (P &lt; 0.05). Consistently, HP sows revealed increased alpha diversity and butyrate-producing genera, as well as fecal butyrate concentration, on gestation d 30; HP sows showed significantly different microbiota community structure with LP sows (P &lt; 0.05) and had markedly higher abundance of Firmicutes (genera Christensenellaceae_R-7_group and Terrisporobacter) which were positively related with litter size on gestation d 110 than LP sows (P &lt; 0.05). In addition, plasma biochemical parameters, plasma cytokines, and fecal microbiota shifted dramatically from gestation d 30 to d 110. Therefore, our findings demonstrated that microbial abundances and community structures differed significantly between sows with different litter sizes and gestation stages, which was associated with changes in plasma biochemical parameters, inflammatory factors, and immunoglobulin. Moreover, these findings revealed that there was a significant correlation between litter size and gut microbiota of sows, and provided a microbial perspective to improve sow reproductive performance in pig production.


2020 ◽  
Author(s):  
Yujing Zhang ◽  
Bing Xie ◽  
Zheng Lv ◽  
Hong Qi ◽  
Jiancheng Zhang ◽  
...  

Abstract Background: Sleep deprivation (SD) is shown to be correlated with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. Methods: In this study, mice were intraperitoneally injected with lipopolysaccharide (LPS) followed by 3 consecutive days of SD. The subdiaphragmatic vagotomy (SDV) was performed 2 weeks before LPS injection. The pseudo germ-free mouse model was created by administering antibiotics for 14 consecutive days, and then fecal microbiota transplant (FMT) was performed by gavaging supernatant from fecal suspension of septic mice with or without SD into pseudo germ-free mice with or without SDV or splenectomy. Splenectomy was performed 14 days prior to antibiotics administration.Results: We found that SD after LPS administration increased the plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), reduced IL-10 plasma leve, increased spleen weight, and promoted pathological injury and IL-6 expression in lung, liver and kidney. Post-septic sleep deprivation had no effects on the diversity of gut microbiota. However, the relative abundance of Proteobacteria and its subgroups were increased in septic mice received SD. Pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors do. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, Splenectomy also abrogated the increase in IL-6 and TNF-α plasma levels and the decrease in IL-10 plasma level in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Conclusions: Taken together, our results suggest that gut microbiota-vagus nerve axis and gut microbiota-spleen axis could play key roles in modulating systemic inflammation induced by SD after LPS administration.


Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2271 ◽  
Author(s):  
Jennifer Gjerde ◽  
Marian Kjellevold ◽  
Lisbeth Dahl ◽  
Torill Berg ◽  
Annbjørg Bøkevoll ◽  
...  

Vitamin D deficiency in pregnant women and their offspring may result in unfavorable health outcomes for both mother and infant. A 25hydroxyvitamin D (25(OH)D) level of at least 75 nmol/L is recommended by the Endocrine Society. Validated, automated sample preparation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were used to determine the vitamin D metabolites status in mother-infant pairs. Detection of 3-Epi25(OH)D3 prevented overestimation of 25(OH)D3 and misclassification of vitamin D status. Sixty-three percent of maternal 25(OH)D plasma levels were less than the recommended level of 25(OH)D at 3 months. Additionally, breastmilk levels of 25(OH)D decreased from 60.1 nmol/L to 50.0 nmol/L between six weeks and three months (p < 0.01). Furthermore, there was a positive correlation between mother and infant plasma levels (p < 0.01, r = 0.56) at 3 months. Accordingly, 31% of the infants were categorized as vitamin D deficient (25(OH)D < 50 nmol/L) compared to 25% if 3-Epi25(OH)D3 was not distinguished from 25(OH)D3. This study highlights the importance of accurate quantification of 25(OH)D. Monitoring vitamin D metabolites in infant, maternal plasma, and breastmilk may be needed to ensure adequate levels in both mother and infant in the first 6 months of infant life.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shintaro Okumura ◽  
Yusuke Konishi ◽  
Megumi Narukawa ◽  
Yuki Sugiura ◽  
Shin Yoshimoto ◽  
...  

AbstractEmerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2 Porphyromonas species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the bacterial metabolite, butyrate. Notably, the invasion of these bacteria is observed in the CRC tissues, coinciding with the elevation of butyrate levels and signs of senescence-associated inflammatory phenotypes. Moreover, although the administration of these bacteria into ApcΔ14/+ mice accelerate the onset of colorectal tumours, this is not the case when bacterial butyrate-synthesis genes are disrupted. These results suggest a causal relationship between Porphyromonas species overgrowth and colorectal tumourigenesis which may be due to butyrate-induced senescence.


2021 ◽  
Vol 15 ◽  
Author(s):  
Xia Cao ◽  
Kevin Liu ◽  
Jun Liu ◽  
Yen-Wenn Liu ◽  
Li Xu ◽  
...  

Inflammation and the gut-brain axis have been implicated in the pathogenesis of autism spectrum disorders (ASDs). To further understand the relationship between aberrant immune responses and dysbiotic features of the gut microbiome in ASD, we enrolled 45 ASD individuals and 41 healthy control subjects with ages ranging from 2 to 19 years. We found that ASD group subjects have significantly higher plasma levels of IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, TNF-β, and IFN-γ when compared to healthy controls (FDR-adjusted p &lt; 0.05). The plasma levels of pro-inflammatory cytokines IFN-γ and IL-6 are found to be further associated with several largely pathogenic gut microbiota uniquely detected in subjects with ASD. Furthermore, the ASD gut microbiome is characterized by reduced levels of several beneficial microbiota, including Bacteroides (FDR-adjusted p &lt; 0.01) and Lachnospiraceae (FDR-adjusted p &lt; 0.001). Analysis of Lachnospiraceae family and genus level taxa suggested that relative abundances of such taxa are negatively correlated with pro-inflammatory signaling cytokines IFN-γ and IL-6, particularly in subjects with severe ASD as defined by CARS (p &lt; 0.05). Several largely pathogenic genera are determined to be associated with the pro-inflammatory cytokines IFN-γ and IL-6 (FDR-adjusted p &lt; 0.1). Additionally, IL-4 is significantly negatively correlated with CARS total score (p &lt; 0.05). Based on such results, we propose that the association between the disturbances of specific cytokines and alterations in gut microbiota abundance observed in children and adolescents with ASD provides additional evidence on the induction of aberrant pro-inflammatory mechanisms in ASD and its early diagnosis.


Microbiome ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Baokun He ◽  
Yuying Liu ◽  
Thomas K. Hoang ◽  
Xiangjun Tian ◽  
Christopher M. Taylor ◽  
...  

Abstract Background Regulatory T cell (Treg) deficiency leads to IPEX syndrome, a lethal autoimmune disease, in Human and mice. Dysbiosis of the gut microbiota in Treg-deficient scurfy (SF) mice has been described, but to date, the role of the gut microbiota remains to be determined. Results To examine how antibiotic-modified microbiota can inhibit Treg deficiency-induced lethal inflammation in SF mice, Treg-deficient SF mice were treated with three different antibiotics. Different antibiotics resulted in distinct microbiota and metabolome changes and led to varied efficacy in prolonging lifespan and reducing inflammation in the liver and lung. Moreover, antibiotics altered plasma levels of several cytokines, especially IL-6. By analyzing gut microbiota and metabolome, we determined the microbial and metabolomic signatures which were associated with the antibiotics. Remarkably, antibiotic treatments restored the levels of several primary and secondary bile acids, which significantly reduced IL-6 expression in RAW macrophages in vitro. IL-6 blockade prolonged lifespan and inhibited inflammation in the liver and lung. By using IL-6 knockout mice, we further identified that IL-6 deletion provided a significant portion of the protection against inflammation induced by Treg dysfunction. Conclusion Our results show that three antibiotics differentially prolong survival and inhibit lethal inflammation in association with a microbiota—IL-6 axis. This pathway presents a potential avenue for treating Treg deficiency-mediated autoimmune disorders.


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