scholarly journals A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiang Yue ◽  
Mingfei Cai ◽  
Bo Xiao ◽  
Qiong Zhan ◽  
Chang Zeng

Background and Aims: Central 5-hydroxytryptamine (5-HT) defects are responsible for the occurrence of sudden unexpected death in epilepsy (SUDEP). The DBA/1 mouse is an animal model of SUDEP since the mouse exhibits audiogenic seizure-induced respiratory arrest (S-IRA). The synthesis of central 5-HT is closely related to the gut microbiota. Moreover, emerging studies suggest a possible role for the microbiota in mitigating seizure likelihood. Based on this, we aimed to explore the effect of a high-tryptophan diet (HTD) on SUDEP as well as the synthesis and metabolism of central 5-HT. Furthermore, we investigated the involvement of the gut microbiota in this process.Methods: All DBA/1 mice were subjected to acoustic stimulation to induce seizures. Only those mice that exhibited S-IRA were randomly assigned to the normal diet (ND) group (n = 39) or HTD group (n = 53). After 1 month of dietary intervention, (1) S-IRA rates were evaluated, (2) the concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the plasma and brain were determined by ultra-high-pressure liquid chromatography, and (3) the fecal flora biodiversity and species composition were analyzed by 16S rDNA microbiota profiling.Results: The S-IRA rate in DBA/1 mice was significantly reduced in the HTD group compared with that in the control group. HTD increased the levels of 5-HT and 5-HIAA in both the telencephalon and midbrain. HTD significantly elevated the species richness and diversity of the gut microbiota. Moreover, there was a significant difference in the gut microbiota composition between the two groups, and the intestinal flora was dominated by Proteobacteria and Actinobacteria after HTD.Conclusions: HTD is efficient in lowering S-IRA rates and elevating the central 5-HT level in DBA/1 mice. The gut microbiota was altered after HTD intervention. The significant increase in Proteobacteria and Actinobacteria may be related to the SUDEP-protective effect of HTD. Our findings shed light on a candidate choice of dietary prevention for SUDEP.

2021 ◽  
Author(s):  
Qiang Yue ◽  
Mingfei Cai ◽  
Bo Xiao ◽  
Qiong Zhan ◽  
Chang Zeng

Abstract Background: Central 5-hydroxytryptamine (5-HT) defects are responsible for the occurrence of audiogenic seizure-induced respiratory arrest (S-IRA) in DBA/1 mice, an animal model of sudden unexpected death in epilepsy (SUDEP). We aimed to explore the effect of a high tryptophan diet (HTD) on SUDEP and its possible mechanism involving 5-HT metabolism via gut microbiota.Methods: Primed animals were randomly assigned to the normal diet (ND) group or HTD group. Before and after diet interventions, 1) S-IRA rates were evaluated, 2) the concentrations of upstream-to-downstream 5-HT metabolites in the plasma and brain were detected by ultra-high-pressure liquid chromatography, and 3) the fecal flora biodiversity and species composition were analysed by 16S rDNA microbiota profiling. Second, antibiotics or probiotics combined with the HTD and S-IRA rates were reassessed.Results: The S-IRA rate in DBA/1 mice was significantly reduced in the HTD group compared with that in control. The HTD obviously increased the levels of tryptophan in the telencephalon and 5-HT and 5-hydroxyindoleacetic acid levels in both the telencephalon and midbrain. The HTD significantly increased the species richness and diversity of gut microbiota. Moreover, there was a significant difference in the gut microbiota composition between the HTD and ND groups. However, antibiotics or probiotics had no synergistic or antagonistic effects on S-IRA reduction mediated by the HTD.Conclusions: An HTD is efficient in lowering S-IRA rates in DBA/1 mice, possibly via modulation of 5-HT metabolism and gut microbiota. Our findings shed light on dietary prevention of SUDEP.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yang Shen ◽  
Xiao Yang ◽  
Gaofei Li ◽  
Jiayu Gao ◽  
Ying Liang

AbstractThe alterations in the gut microbiota have been reported to be correlated with the development of depression. The purpose of this study was to investigate the changes of intestinal microbiota in depressed patients after antidepressant treatment. We recruited 30 MDD patients (MDD group) and 30 healthy controls (control group). The MDD group received individualized treatment with escitalopram at a maximum dose of 20 mg/day. After depressive symptoms improved to a HAMD scale score > 50%, a fecal sample was collected again and used as the follow-up group. The differences of gut microbiota between patients and controls, the characteristics of gut microbiota under treatment and the potential differences in metabolic functions were thus investigated. The Firmicutes/Bacteroidetes ratio was significantly different within three groups, and the ratio of follow-up group was significantly lower than those of the other two groups. Alpha diversity was significantly higher in MDD group than those of the other groups, and the alpha diversity was not significantly different between control and follow-up groups. The beta diversity of some patients resembled participants in the control group. The metabolic function of gut microbiota after treatment was still different from that of the control group. This study suggests that the intestinal flora of depressed patients has a tendency to return to normal under escitalopram treatment.


Author(s):  
Rizka Veni ◽  
Awal Prasetyo ◽  
Muflihatul Muniroh

This study aims to analyze the effect of combination of motor vehicle particular matter exposure and high-fat diet in kidney histopathology, creatinine levels, and MDA levels in Wistar rats. This study used a posttest-only control group design. Eighteen healthy male Wistar rats were divided into three groups. The intervention groups received motor vehicle fume exposure for 100 s with normal diet (X1) or high-fat diet (X2), and the control group received no exposure (C). Data analysis was processed with a SPSS 25.0 computer program by using the one-way ANOVA test followed by post hoc LSD. The degree of kidney histopathological damage showed significant differences between the X1 and X2 groups when compared with the control group (p < 0.05). The results of the creatinine level examination found a significant difference between the X2 and C groups (p < 0.05) and the treatment groups X1 and X2 (p < 0.05). The results of kidney MDA level examination showed a significant difference between the treatment groups (X1 and X2) and the control group (p < 0.05). The combination of particular matter of motor vehicle fumes exposure and high-fat diet could induce kidney damage through histopathological change and increased creatinine levels and kidney MDA levels in Wistar rats.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Song ◽  
Li-Ying Sun ◽  
Zhi-Jun Zhu ◽  
Lin Wei ◽  
Wei Qu ◽  
...  

Background and AimsBiliary atresia (BA) is an idiopathic neonatal cholestasis and is the most common indication in pediatric liver transplantation (LT). Previous studies have suggested that the gut microbiota (GM) in BA is disordered. However, the effect of LT on gut dysbiosis in patients with BA has not yet been elucidated.MethodsPatients with BA (n = 16) and healthy controls (n = 10) were recruited. In the early life of children with BA, Kasai surgery is a typical procedure for restoring bile flow. According to whether BA patients had previously undergone Kasai surgery, we divided the post-LT patients into the with-Kasai group (n = 8) and non-Kasai group (n = 8). Fecal samples were collected in both the BA and the control group; among BA patients, samples were obtained again 6 months after LT. A total of 40 fecal samples were collected, of which 16 were pre-LT, 14 were post-LT (8 were with-Kasai, 6 were non-Kasai), and 10 were from the control group. Metagenomic sequencing was performed to evaluate the GM.ResultsThe Kruskal-Wallis test showed a statistically significant difference in the number of genes between the pre-LT and the control group, the pre-LT and the post-LT group (P &lt; 0.05), but no statistical difference between the post-LT and the control group. Principal coordinate analysis also showed that the microbiome structure was similar between the post-LT and control group (P &gt; 0.05). Analysis of the GM composition showed a significant decrease in Serratia, Enterobacter, Morganella, Skunalikevirus, and Phifllikevirus while short chain fatty acid (SCFA)-producing bacteria such as Roseburia, Blautia, Clostridium, Akkermansia, and Ruminococcus were increased after LT (linear discriminant analysis &gt; 2, P &lt; 0.05). However, they still did not reach the normal control level. Concerning functional profiles, lipopolysaccharide metabolism, multidrug resistance, polyamine biosynthesis, GABA biosynthesis, and EHEC/EPEC pathogenicity signature were more enriched in the post-LT group compared with the control group. Prior Kasai surgery had a specific influence on the postoperative GM.ConclusionLT partly improved the GM in patients with BA, which provided new insight into understanding the role of LT in BA.


2021 ◽  
Author(s):  
Lingxiong Chai ◽  
Qun Luo ◽  
Kedan Cai ◽  
Kaiyue Wang ◽  
Binbin Xu

Abstract Background: IgA nephropathy(IgAN)) is the common pathological type of glomerular diseases. The role of gut microbiota in mediating "gut-IgA nephropathy" has not received sufficient attention in the previous studies. The purpose of this study was to investigate the changes of fecal short-chain fatty acids(SCFAs), a metabolite of the intestinal microbiota, in patients with IgAN and its correlation with intestinal flora and clinical indicators, and to further investigate the role of the gut-renal axis in IgAN.Methods: There were 29 patients with IgAN and 29 normal control subjects recruited from January 2018 to May 2018. The fresh feces were collected. The fecal SCFAs were measured by gas chromatography/mass spectrometry and gut microbiota was analysed by16S rDNA sequences, followed by estimation of α- and β-diversity. Correlation analysis was performed using the spearman’s correlation test between SCFAs and gut microbiota. Results:The levels of acetic acid, propionic acid, butyric acid, isobutyric acid and caproic acid in the IgAN patients were significantly reduced compared with control group(P<0.05). Butyric acid(r=-0.336, P=0.010) and isobutyric acid(r=-0.298, P=0.022) were negatively correlated with urea acid; butyric acid(r=-0.316, P=0.016) was negatively correlated with urea nitrogen; caproic acid(r=-0.415,P=0.025) showed negative correlation with 24-h urine protein level.Exemplified by the results of α-diversity and β-diversity, the intestinal flora of IgAN patients was significantly different from that of the control group. Acetic acid was positively associated with c_Clostridia(r=0.357, P=0.008), o_Clostridiales(r=0.357, P=0.008) and g_Eubacterium_coprostanoligenes_group(r=0.283, P=0.036). Butyric acid was positively associated with g_Alistipes (r=0.278, P=0.040). The relative abundance of those were significantly decreased in IgAN group compared to control group.Conclusion: The levels of fecal SCFAs in the IgAN patients were reduced, and correlated with clinical parameters and gut microbiota, which may be involved in the pathogenesis of IgAN, and this finding may provide a new therapeutic approach.


2020 ◽  
Author(s):  
Yue Shen ◽  
HaiXiang Ma ◽  
XiTing Lian ◽  
LeYuan Gu ◽  
Qian Yu ◽  
...  

AbstractSudden unexpected death in epilepsy (SUDEP) is the fatal cause leading to the death of epilepsy patients with anti-epileptic drug resistance. However, the underlying mechanism of SUDEP remains to be elusive. Our previous study demonstrated that enhancement of serotonin (5-HT) synthesis by intraperitoneal (IP) injection of 5-hydroxytryptophan in brain significantly reduced the incidence of seizure-induced respiratory arrest (S-IRA) in DBA/1 mice SUDEP models. Given that 5-HT2A receptor (5-HT2AR) acts an important role in mediating respiration system in brain, we hypothesized that 5-HT2AR is of great significance to modulate S-IRA and SUDEP. To test this hypothesis, we examined whether the decreased incidence S-IRA evoked by either acoustic stimulation or PTZ by blocking 5-HT2AR by administration with ketanserin (KET), a selective antagonist of 5HT2AR, in DBA/1 mice SUDEP models to test the role of 5-HT2AR modulating S-IRA. Our results suggested that the decreased incidence of S-IRA by 5-Hydroxytryptophan (5-HTP), a precursor for central nervous system (CNS) serotonin (5-HT) synthesis, was significantly reversed by IP and intracerebroventricularly (ICV) injection of ketanserin in our models. Thus, our data suggested that 5-HT2AR in the brain may be a potential and specific target to prevent SUDEP.


2021 ◽  
Vol 9 ◽  
Author(s):  
Yan Sun ◽  
Lei Li ◽  
Jiayu Song ◽  
Wei Mao ◽  
Kaihao Xiao ◽  
...  

Background: Accumulating evidence suggests a connection between the gut microbiota and neonatal diseases. Hypoxia may play an important role in the intestinal lesions in neonates.Objective: This study aims to determine whether the gut microbiota differs between intrauterine hypoxic rats and healthy controls and to identify the factors that influence the changes in the gut microbiota.Methods: We constructed an intrauterine hypoxia model in rats and collected the intestinal contents of intrauterine hypoxic newborn rats and normal newborn rats within 4 h and on the seventh day after birth. They were divided them into the intrauterine hypoxia first-day group (INH1), intrauterine hypoxia seventh-day group (INH7), normal first-day group (NOR1), and normal seventh-day group (NOR7). The contents of the intestines were sequenced with 16S rRNA sequencing, the sequencing results were analyzed for biological information, and the differences in the diversity, richness, and individual taxa among the groups were analyzed.Results: The abundance of the gut microbiota of neonatal rats with intrauterine hypoxia was higher than that of the control group rats. Intrauterine hypoxia altered the structural composition of the gut microbiota in neonatal rats. The INH1 group showed increased species richness, phylogenetic diversity, and β-diversity, and altered relative abundance in several taxa compared to those in the control group. The differences in the microbiota among the four groups were significantly higher than those within the group, and the differences in the abundance and diversity of the INH7 and NOR7 groups decreased after 7 days of suckling. Functional analysis based on the Cluster of Orthologous Groups (COG) suggested that 23 functional COG categories. There was no significant difference in the functional categories between the hypoxia group and the normal group.Conclusion: Intrauterine hypoxia changed the initial colonization of the gut microbiota in neonatal rats. It could increase the species richness and β-diversity of the gut microbiota, and altered relative abundances of several taxa.


2021 ◽  
Author(s):  
Michaela Kaiserova ◽  
Monika Chudackova ◽  
Hana Prikrylova Vranova ◽  
Katerina Mensikova ◽  
Anetta Kastelikova ◽  
...  

Background: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. Methods: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal degeneration (CBD) patients, and 31 controls. We also compared the values in depressed and non-depressed patients. Results: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 µg/l, in MSA 13.6 µg/l vs. 24.3 µg/l in controls; P=0.0008 in PD, P=0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBD compared to the control group (median in PSP 22.7 µg/l, in CBD 18.7 µg/l vs. 24.3 µg/l in controls; P= 1 in both PSP and CBD). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, P<0.0001). Conclusions: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD, however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD, MSA) than in tauopathies (PSP, CBS).


2020 ◽  
pp. 1-13
Author(s):  
Samantha L Dawson ◽  
Mohammadreza Mohebbi ◽  
Jeffrey M Craig ◽  
Phillip Dawson ◽  
Gerard Clarke ◽  
...  

Abstract Objective: To evaluate the hypothesis that a perinatal educational dietary intervention focused on ‘eating for the gut microbiota’ improves diet quality of pregnant women pre- and postnatally. Design: The Healthy Parents, Healthy Kids study is a prospectively registered randomised controlled trial designed to evaluate the efficacy of a dietary intervention in altering the maternal and infant gut microbiota and improving perinatal diet quality. Eligible pregnant women were randomised to receive dietary advice from their healthcare provider or to additionally receive a three session dietary intervention. Dietary data were collected at gestation weeks 26, 31, 36 and postnatal week 4. Outcome measures were diet quality, dietary variety, prebiotic and probiotic food intakes, energy, fibre, saturated fat and discretionary food intakes. Between-group differential changes from baseline before and after birth in these dietary measures were assessed using generalised estimating equations. Setting: Melbourne, Australia. Participants: Healthy pregnant women from gestation week 26. Results: Forty-five women were randomised (twenty-two control, twenty-three intervention). Compared with the control group, the intervention group improved diet quality prior to birth (5·66 (95 % CI 1·65, 9·67), Cohen’s d: 0·82 (se 0·33)). The intervention improved dietary variety (1·05 (95 % CI 0·17, 1·94), d: 0·66 (se 0·32)) and increased intakes of prebiotic (0·8 (95 % CI 0·27, 1·33), d: 0·91 (se 0·33)) and probiotic foods (1·05 (95 % CI 0·57, 1·53), d: 1·3(se 0·35)) over the whole study period compared with the control group. Conclusion: A dietary intervention focused on ‘eating for the gut microbiota’ can improve aspects of perinatal diet quality during and after pregnancy.


2020 ◽  
Vol 8 (1) ◽  
pp. 94 ◽  
Author(s):  
Alejandra Chávez-Carbajal ◽  
María Luisa Pizano-Zárate ◽  
Fernando Hernández-Quiroz ◽  
Guillermo Federico Ortiz-Luna ◽  
Rosa María Morales-Hernández ◽  
...  

In this work, we studied 217 Mexican subjects divided into six groups with different stages of glucose intolerance: 76 Controls (CO), 54 prediabetes (PRE), 14 T2D no medication (T2D−No−M), 14 T2D with Metformin (T2D−M), 22 T2D with polypharmacy (T2D−P), and 37 T2D with polypharmacy and insulin (T2D−P+I). We aimed to determine differences in the gut microbiota diversity for each condition. At the phylum level, we found that Firmicutes and Bacteroidetes outline major changes in the gut microbiota. The gut bacterial richness and diversity of individuals in the T2D−No−M group were lesser than other groups. Interestingly, we found a significant difference in the beta diversity of the gut microbiota among all groups. Higher abundance was found for Comamonadaceae in PRE, and Sutterella spp. in T2D−No−M. In addition, we found associations of specific microbial taxa with clinical parameters. Finally, we report predicted metabolic pathways of gut microbiota linked to T2D−M and PRE conditions. Collectively, these results indicate that each group has specific predicted metabolic characteristics and gut bacteria populations for each phenotype. The results of this study could be used to define strategies to modulate gut microbiota through noninvasive treatments, such as dietary intervention, probiotics or prebiotics, and to improve glucose tolerance of individuals with prediabetes or T2D.


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