scholarly journals Fluoxetine-induced alteration of murine gut microbial community structure: evidence for a microbial endocrinology-based mechanism of action responsible for fluoxetine-induced side effects

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6199 ◽  
Author(s):  
Mark Lyte ◽  
Karrie M. Daniels ◽  
Stephan Schmitz-Esser
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Side Effects ◽  
Gut Microbiota ◽  
Microbial Communities ◽  
Time Course ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Sequence Data ◽  
Rrna Gene ◽  
Dosing Regimen

Background Depression and major depressive disorder affect 25% of the population. First line treatment utilizing selective serotonin reuptake inhibitors (SSRIs) have met with limited success due to well-recognized negative side effects which include weight gain or loss. This inability to control unwanted side effects often result in patients stopping their antidepressant medications. The mechanisms underlying the failure of SSRIs are incompletely understood. Methods Male CF-1 mice (5 weeks of age, N = 10 per group) were per orally administered fluoxetine (20 mg per kg body weight) or diluent daily for 29 days. During this time fecal specimens were collected at three defined time points (0, 15 and 29 days). At the conclusion of the 29-day dosing regimen, animals were subjected to two behavioral assessments. For bacterial identification of the microbiota, 16S rRNA gene sequencing was performed on 60 fecal specimens (three specimens per mouse time course, N = 20 mice) using Illumina MiSeq. Analysis of community sequence data was done using mothur and LEfSe bioinformatic software packages. Results Daily per oral administration of fluoxetine for 29 days to male mice resulted in a significant, time dependent, alteration in microbial communities accompanying changes in body weight. The calculated species richness and diversity indicators of the murine fecal microbial communities were inconsistent and not significantly different between the groups. Among the phylotypes decreased in abundance due to fluoxetine administration were Lactobacillus johnsonii and Bacteroidales S24-7 which belong to phyla associated with regulation of body mass. The observed changes in body weight due to fluoxetine administration mimicked the dramatic shifts in weight gain/loss that has been observed in humans. Further, at the conclusion of the 29-day dosing regimen fluoxetine-dosed animals evidenced a mild anxiogenic-like behavior. Discussion We report that the most widely used antidepressant, fluoxetine, which is an SSRI-type drug, results in the selective depletion of gut microbiota, specifically the Lactobacilli which are involved in the regulation of body weight. Concomitantly, fluoxetine administration increases the abundance of phylotypes related to dysbiosis. Since Lactobacilli have been previously shown to possess a known biogenic amine transporter that regulates the uptake of fluoxetine, it is proposed that a microbial endocrinology-based mechanistic pathway is responsible for the ability of SSRIs to selectively negatively impact beneficial microbiota. The results of this study therefore suggest that the negative clinical side effects due to fluoxetine administration may be due to alterations in gut microbiota. Further, the data also suggests that supplementation of bacterial genera directly affected by fluoxetine administration may prove useful in ameliorating some of the well-known side effects of chronic fluoxetine administration such as weight alterations.

scholarly journals DISTINCT INTESTINAL MICROBIAL COMMUNITIES OF TWO SYMPATRIC ANADROMOUS ARCTIC SALMONIDS AND THE EFFECTS OF MIGRATION AND FEEDING

2020 ◽  
Author(s):  
Geraint Element ◽  
Katja Engel ◽  
Josh Neufeld ◽  
John Casselman ◽  
Peter Van Coeverden de Groot ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Microbial Communities ◽  
Sequence Data ◽  
Salvelinus Alpinus ◽  
Microbial Community Composition ◽  
Arctic Char ◽  
Microbial Consortia ◽  
Rrna Gene ◽  
Lake Whitefish ◽  
Abiotic And Biotic Factors

Although intestinal microbial communities from anadromous Arctic char (Salvelinus alpinus) in Kitikmeot, Nunavut, differ depending on the timing and location of capture, determinants of gut microbiota in other wild Arctic salmonids are largely unknown. Using high-throughput 16S rRNA gene sequence data, we compared intestinal microbiota from Arctic char to those from a related and sympatric salmonid, lake whitefish (Coregonus clupeaformis). Shifts in lake whitefish gut microbial community composition were observed between brackish and freshwaters, similar to impacts of salinity reported previously for Arctic char. Despite these similarities, gut community profiles for the two salmonids differed, whitefish having higher diversities and increased proportions of taxa affiliated with potential pathogens. Geography seemed to have a greater impact on freshwater whitefish gut microbiota than on corresponding Arctic char. Additionally, microbiota diversity was significantly more affected by feeding behavior in whitefish compared to sympatric Arctic char. Since sampled whitefish were at their northern range limits and grew slowly, we speculate that they, and their microbial consortia, could be more vulnerable to certain abiotic and biotic factors than Arctic char, which are well adapted to conditions found in these high latitude environments and have the most northerly distribution of any freshwater fish.

Attitudes about Antidepressants: Influence of Information about Weight-Related Side Effects

2000 ◽  
Vol 90 (2) ◽  
pp. 453-456 ◽  
Author(s):  
Thomas F. Cash ◽  
Melissa A. Brown
Keyword(s):  
Weight Loss ◽  
Body Image ◽  
Body Weight ◽  
Weight Gain ◽  
Side Effects ◽  
College Women ◽  
Antidepressant Drugs ◽  
Antidepressant Medications ◽  
Body Image Ideals ◽  
Clinical Populations

Antidepressant drugs are frequently prescribed for women and have various side effects, including potential effects on body weight. This experiment examined the effects of information about the weight-related side effects of antidepressants on women's attitudes toward the drugs. 60 college women were randomly assigned to read about one of two drugs, fluoxetine (Prozac) or Imipramine (Tofranil). Participants were either told or not told about veridical weight-related side effects, namely, weight loss for Prozac and weight gain for Tofranil. As hypothesized, weight-gain information lowered the personal acceptability of Tofranil, and weight-loss information enhanced the acceptability of Prozac. Although research with clinical populations is required, undergraduate women's decisions about the use of antidepressant medications may be influenced by societal body-image ideals.

scholarly journals Ontogenetic Differences in Dietary Fat Influence Microbiota Assembly in the Zebrafish Gut

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Sandi Wong ◽  
W. Zac Stephens ◽  
Adam R. Burns ◽  
Keaton Stagaman ◽  
Lawrence A. David ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Microbial Communities ◽  
Dietary Fat ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Ideal Model ◽  
Surrounding Environment ◽  
Animal Hosts ◽  
The Relationship ◽  
Gut Microbiota Composition

ABSTRACT Gut microbiota influence the development and physiology of their animal hosts, and these effects are determined in part by the composition of these microbial communities. Gut microbiota composition can be affected by introduction of microbes from the environment, changes in the gut habitat during development, and acute dietary alterations. However, little is known about the relationship between gut and environmental microbiotas or about how host development and dietary differences during development impact the assembly of gut microbiota. We sought to explore these relationships using zebrafish, an ideal model because they are constantly immersed in a defined environment and can be fed the same diet for their entire lives. We conducted a cross-sectional study in zebrafish raised on a high-fat, control, or low-fat diet and used bacterial 16S rRNA gene sequencing to survey microbial communities in the gut and external environment at different developmental ages. Gut and environmental microbiota compositions rapidly diverged following the initiation of feeding and became increasingly different as zebrafish grew under conditions of a constant diet. Different dietary fat levels were associated with distinct gut microbiota compositions at different ages. In addition to alterations in individual bacterial taxa, we identified putative assemblages of bacterial lineages that covaried in abundance as a function of age, diet, and location. These results reveal dynamic relationships between dietary fat levels and the microbial communities residing in the intestine and the surrounding environment during ontogenesis. IMPORTANCE The ability of gut microbiota to influence host health is determined in part by their composition. However, little is known about the relationship between gut and environmental microbiotas or about how ontogenetic differences in dietary fat impact gut microbiota composition. We addressed these gaps in knowledge using zebrafish, an ideal model organism because their environment can be thoroughly sampled and they can be fed the same diet for their entire lives. We found that microbial communities in the gut changed as zebrafish aged under conditions of a constant diet and became increasingly different from microbial communities in their surrounding environment. Further, we observed that the amount of fat in the diet had distinct age-specific effects on gut community assembly. These results reveal the complex relationships between microbial communities residing in the intestine and those in the surrounding environment and show that these relationships are shaped by dietary fat throughout the life of animal hosts.

scholarly journals Antidepressant-induced jitteriness/anxiety syndrome: systematic review

2009 ◽  
Vol 194 (6) ◽  
pp. 483-490 ◽  
Author(s):  
Lindsey I. Sinclair ◽  
David M. Christmas ◽  
Sean D. Hood ◽  
John P. Potokar ◽  
Andrea Robertson ◽  
...  
Keyword(s):  
Side Effects ◽  
Anxiety Disorders ◽  
Time Course ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Rating Scales ◽  
Antidepressant Treatment ◽  
Incidence Rates ◽  
Conclusive Evidence ◽  
Response To Treatment ◽  
Robust Evidence

BackgroundEarly worsening of anxiety, agitation and irritability are thought to be common among people commencing antidepressants, especially for anxiety disorders. This phenomenon, which may be termed jitteriness/anxiety syndrome, is cited as an explanation for early treatment failure and caution in using selective serotonin reuptake inhibitors (SSRIs). However, we believe that it is inconsistently defined and that robust evidence to support the phenomenon is lacking.AimsTo review systematically all evidence relating to jitteriness/ anxiety syndrome to identify: constituent symptoms; medications implicated; disorders in which it was reported; incidence; time course; management strategies; relationship of this syndrome to therapeutic response; distinction between syndrome and akathisia; relationship between syndrome and suicide; and genetic predispositions.MethodA systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome.ResultsOf 245 articles identified, 107 articles were included for review. No validated rating scales for jitteriness/anxiety syndrome were identified. There was no robust evidence that the incidence differed between SSRIs and tricyclic antidepressants, or that there was a higher incidence in anxiety disorders. Published incidence rates varied widely from 4 to 65% of people commencing antidepressant treatment. Common treatment strategies for this syndrome included a slower titration of antidepressant and the addition of benzodiazepines. Conclusive evidence for the efficacy of these strategies is lacking. There was conflicting and inconclusive evidence as to whether the emergence of this syndrome had a predictive value on the response to treatment. It appears to be a separate syndrome from akathisia, but evidence for this assertion was limited. The effect of jitteriness/anxiety syndrome on suicide rates has not been evaluated. Three studies examined genetic variations and side-effects from treatment, but none was specifically designed to assess jitteriness/anxiety syndrome.ConclusionsJitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.

scholarly journals Prolonged intake of desloratadine: mesenteric lymphatic vessel dysfunction and development of obesity/metabolic syndrome

2019 ◽  
Vol 316 (1) ◽  
pp. G217-G227 ◽  
Author(s):  
Olga Y. Gasheva ◽  
Irina Tsoy Nizamutdinova ◽  
Laura Hargrove ◽  
Cassidy Gobbell ◽  
Maria Troyanova-Wood ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Body Weight ◽  
Weight Gain ◽  
Side Effects ◽  
Lymphatic Vessel ◽  
Fasting Blood Glucose ◽  
Lymphatic Vessels ◽  
The United States ◽  
Lymph Flow ◽  
The Body

This study aimed to establish mechanistic links between the prolonged intake of desloratadine, a common H1 receptor blocker (i.e., antihistamine), and development of obesity and metabolic syndrome. Male Sprague-Dawley rats were treated for 16 wk with desloratadine. We analyzed the dynamics of body weight gain, tissue fat accumulation/density, contractility of isolated mesenteric lymphatic vessels, and levels of blood lipids, glucose, and insulin, together with parameters of liver function. Prolonged intake of desloratadine induced development of an obesity-like phenotype and signs of metabolic syndrome. These alterations in the body included excessive weight gain, increased density of abdominal subcutaneous fat and intracapsular brown fat, high blood triglycerides with an indication of their rerouting toward portal blood, high HDL, high fasting blood glucose with normal fasting and nonfasting insulin levels (insulin resistance), high liver/body weight ratio, and liver steatosis (fatty liver). These changes were associated with dysfunction of mesenteric lymphatic vessels, specifically high lymphatic tone and resistance to flow together with diminished tonic and abolished phasic responses to increases in flow, (i.e., greatly diminished adaptive reserves to respond to postprandial increases in lymph flow). The role of nitric oxide in this flow-dependent adaptation was abolished, with remnants of these responses controlled by lymphatic vessel-derived histamine. Our current data, considered together with reports in the literature, support the notion that millions of the United States population are highly likely affected by underevaluated, lymphatic-related side effects of antihistamines and may develop obesity and metabolic syndrome due to the prolonged intake of this medication. NEW & NOTEWORTHY Prolonged intake of desloratadine induced development of obesity and metabolic syndrome associated with dysfunction of mesenteric lymphatic vessels, high lymphatic tone, and resistance to flow together with greatly diminished adaptive reserves to respond to postprandial increases in lymph flow. Data support the notion that millions of the USA population are highly likely affected by underevaluated, lymphatic-related side effects of antihistamines and may develop obesity and metabolic syndrome due to the prolonged intake of this medication.

scholarly journals Assessment of Microbial Communities by Graph Partitioning in a Study of Soil Fungi in Two Alpine Meadows

2009 ◽  
Vol 75 (18) ◽  
pp. 5863-5870 ◽  
Author(s):  
L. Zinger ◽  
E. Coissac ◽  
P. Choler ◽  
R. A. Geremia
Keyword(s):  
Microbial Communities ◽  
Graph Partitioning ◽  
Sequence Data ◽  
Large Subunit ◽  
Fungal Communities ◽  
Rrna Gene ◽  
Data Sets ◽  
Alignment Algorithm ◽  
Single Linkage ◽  
Phylogenetic Structure

ABSTRACT Understanding how microbial community structure and diversity respond to environmental conditions is one of the main challenges in environmental microbiology. However, there is often confusion between determining the phylogenetic structure of microbial communities and assessing the distribution and diversity of molecular operational taxonomic units (MOTUs) in these communities. This has led to the use of sequence analysis tools such as multiple alignments and hierarchical clustering that are not adapted to the analysis of large and diverse data sets and not always justified for characterization of MOTUs. Here, we developed an approach combining a pairwise alignment algorithm and graph partitioning by using MCL (Markov clustering) in order to generate discrete groups for nuclear large-subunit rRNA gene and internal transcript spacer 1 sequence data sets obtained from a yearly monitoring study of two spatially close but ecologically contrasting alpine soils (namely, early and late snowmelt locations). We compared MCL with a classical single-linkage method (Ccomps) and showed that MCL reduced bias such as the chaining effect. Using MCL, we characterized fungal communities in early and late snowmelt locations. We found contrasting distributions of MOTUs in the two soils, suggesting that there is a high level of habitat filtering in the assembly of alpine soil fungal communities. However, few MOTUs were specific to one location.

scholarly journals Relationships between pharmacotherapy-induced metabolic changes and improved psychopathology in schizophrenia: data from a mirtazapine and first-generation antipsychotics combination trial

2013 ◽  
Vol 16 (7) ◽  
pp. 1661-1666 ◽  
Author(s):  
Viacheslav Terevnikov ◽  
Jan-Henry Stenberg ◽  
Jari Tiihonen ◽  
Evgeni Chukhin ◽  
Marina Joffe ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Side Effects ◽  
First Generation ◽  
Metabolic Effects ◽  
Open Label ◽  
Double Blind ◽  
Cholesterol Levels ◽  
Syndrome Scale ◽  
Negative Syndrome

Abstract Clinical efficacy and metabolic side-effects of antipsychotics seem to correlate with each other. In this study, interrelationship of similar metabolic effects of mirtazapine and its earlier reported desirable effects on psychopathology in first-generation antipsychotics (FGAs)-treated schizophrenia were explored. Symptomatic FGAs-treated patients with schizophrenia received a 6-wk double-blind treatment with add-on mirtazapine (n = 20) or placebo (n = 16), followed by a 6-wk open-label mirtazapine treatment. Mirtazapine (but not placebo) induced an increase in body weight and cholesterol levels. The latter was associated with a clinical improvement in all (sub)scales of the Positive and Negative Syndrome Scale [PANSS; an increase of cholesterol by 1 mmol/l predicted 7 points reduction on the PANSS total score (r = 0.85, p = 0.001)]. In schizophrenia, mirtazapine-induced weight gain and increase of total cholesterol are associated with the improved efficacy of mirtazapine-FGAs combination – a novel observation with possible clinical and theoretical implications.

scholarly journals Fluoxetine effect on gestation and fetal development

2014 ◽  
Vol 60 (4) ◽  
pp. 157-159
Author(s):  
Bianca Eugenia Ösz ◽  
C. E. Vari ◽  
Maria Dogaru
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Fetal Development ◽  
Wistar Rats ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Gravid Uterus ◽  
Control Group ◽  
Increased Risk ◽  
Female Wistar Rats ◽  
In Pregnancy

Abstract The prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) is very controversial. There is no conclusive evidence for increased risk of malformations after SSRI use in pregnancy. The aim of the study was to determine how fluoxetine is affecting gestation and fetal development in rats. Twenty sexually mature female Wistar rats weighting between 250-260 g received 20 mg/kg body weight fluoxetine from the first day of gestation and during the entire gestation period.The drug was administered by oral route. Healthy, primipareus animals were selected along with 20 female Wistar rats, as control group. Mature males were caged with virgin females for an entire week. Rat’s behaviour during gestation, after birth and rats body weight was examined. The number of healthy pups was also noted. The females not giving birth after 21 days to any pup were anesthetized (halothane through gas scavenging apparatus untilled death) and the gravid uterus were dissected out and examined. Compared to the controlled group, in which weight gain was more significant, the animals from the experimental group had a slight increase in body weight. The weight gain normally induced by gestation, is less significant in fluoxetine treated rats due to the increase serotonin levels in the brain. The uteri examination of pregnant rats showed an increase in the number of dead and resorbed rat embryos. Preclinical studies suggest that the inclusion of fluoxetine in pregnancy category C is justified and the appropriateness of its administration in pregnancy is still an unresolved issue.

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