Journal Article Annotations
2019, 4th Quarter
Annotations by Rebecca Anthony, MD, Jessica Wang, DO, Natalia Ortiz, MD
- Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain-gut axis.
- Association of Alterations in Intestinal Microbiota With Impaired Psychological Function in Patients With Inflammatory Bowel Diseases in Remission.
- Psychiatric medication use and weight outcomes one year after bariatric surgery.
PUBLICATION #1 — GI Psychiatry
Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain-gut axis.
Kohei Takahashi, Osamu Nakagawasai, Wataru Nemoto, Takayo Odaira, Wakana Sakuma, Hiroshi Onogi, Hiroaki Nishijima, Ryuji Furihata, Yukio Nemoto, Hiroyuki Iwasa, Koichi Tan-No and Takeshi Tadano
Patients with inflammatory bowel disease (IBD), including those with ulcerative colitis and Crohn’s disease, have higher rates of psychiatric disorders, such as depression and anxiety; however, the mechanism of psychiatric disorder development remains unclear. Mice with IBD induced by dextran sulfate sodium (DSS) in drinking water exhibit depressive-like behavior. The presence of Lactobacillus in the gut microbiota is associated with major depressive disorder. Therefore, we examined whether Enterococcus faecalis 2001 (EF-2001), a biogenic lactic acid bacterium, prevents DSS-induced depressive-like behavior and changes in peripheral symptoms.
We evaluated colon inflammation and used the tail suspension test to examine whether EF-2001 prevents IBD-like symptoms and depressive-like behavior in DSS-treated mice. The protein expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), X-linked inhibitor of apoptosis protein (XIAP), and cleaved caspase-3 in the rectum and hippocampus was assessed by western blotting. Hippocampal neurogenesis, altered nuclear factor-kappa B (NFκB) p65 morphometry, and the localization of activated NFκB p65 and XIAP were examined by immunohistochemistry.
Treatment with 1.5% DSS for 7 days induced IBD-like pathology and depressive-like behavior, increased TNF-α and IL-6 expression in the rectum and hippocampus, activated caspase-3 in the hippocampus, and decreased hippocampal neurogenesis. Interestingly, these changes were reversed by 20-day administration of EF-2001. Further, EF-2001 administration enhanced NFκB p65 expression in the microglial cells and XIAP expression in the hippocampus of DSS-treated mice.
EF-2001 prevented IBD-like pathology and depressive-like behavior via decreased rectal and hippocampal inflammatory cytokines and facilitated the NFκB p65/XIAP pathway in the hippocampus. Our findings suggest a close relationship between IBD and depression.
Antidepressant; Apoptosis; EF-2001; Inflammatory bowel disease; Neurogenesis; Neuroinflammation
The authors use a well-characterized mouse model for inflammatory bowel disease (Dextran sulphate sodium fed mice) to build off of previous reports that these DSS-treated mice exhibit decreased hippocampal neurogenesis and behaviors consistent with anxiety and depression. The authors sought to use a lactic acid bacterium (Enterococcus faecalis 2001) previously shown to attenuate inflammatory cytokines and protect against apoptosis to examine whether its administration in DSS treated, IBD-model mice could alter depressive-like behavior and underlying inflammation. It was found that EF-2001 administration for 20 days reversed both colitis symptoms and prolonged immobility time. Additionally, EF-2001 administration in DSS mice was found to reverse increased levels of TNF-aand IL-6 in rectal and hippocampal tissue, attenuate reduced neurogenesis in hippocampus, and increase activation of cells responsible for controlling apoptosis in the hippocampus. Taken together, this suggests EF-2001 may have an antidepressant effect via control of pro-inflammatory cytokines and maintenance of hippocampal neurogenesis.
Strength and weaknesses:
As an animal study, strengths lie in the ability to examine inflammatory markers directly in the hippocampus and the ability to administer experimental disease modifiers. Weaknesses include using rodent models for mimicking disease, which often lack the complexity of the underlying condition in terms of genetic and environmental factors.
There is still a dearth of data regarding treatment of depression in IBD, with lack of strong evidence thus far for psychotherapy or traditional antidepressants. Additionally, some evidence has pointed to bi-directional involvement of the brain-gut axis in IBD, but this remains an ongoing area of study. This study serves to add to the understanding of linkage between altered neurogenesis and depression in pro-inflammatory conditions and may lead to better potential interventions for psychological treatment in the future.
Type of study:
(http://ebm.bmj.com/content/early/2016/06/23/ebmed-2016-110401): basic science
PUBLICATION #2 — GI Psychiatry
Association of Alterations in Intestinal Microbiota With Impaired Psychological Function in Patients With Inflammatory Bowel Diseases in Remission.
Fabienne Humbel, Jessica Harrell Rieder, Yannick Franc, Pascal Juillerat, Michael Scharl, Benjamin Misselwitz, Philipp Schreiner, Stefan Begré, Gerhard Rogler, Roland von Känel, Bahtiyar Yilmaz, and Luc Biedermann, on behalf of the Swiss IBD Cohort Study Group
Abstract: Clin Gastroenterol Hepatol. 2019 Sep 20. pii: S1542-3565(19)31028-6. doi: 10.1016/j.cgh.2019.09.022. (Epub ahead of print)
BACKGROUND & AIMS:
Depression and anxiety are frequent comorbidities with inflammatory bowel diseases (IBD). Alterations to the intestinal microbiome promote not only intestinal inflammation but also psychologic function. We studied the interactions between the composition of the intestinal microbiota and psychological outcomes in patients with IBD in Switzerland.
We performed a prospective study of psychological comorbidities and quality of life (QoL) in 171 participants in the Swiss IBD Cohort Study with IBD in remission. Participants complete the Hospital Anxiety and Depression Scale, Perceived Stress Questionnaire, the 36-Item Short Form Survey, and the IBD QoL Questionnaire. Microbes were collected from intestinal biopsies and analyzed by 16S rRNA high-throughput sequencing.
Microbiomes of patients with higher perceived stress had significantly lower alpha diversity. Anxiety and depressive symptoms were significantly associated with beta diversity. We found a negative correlation between psychological distress and abundance of Clostridia, Bacilli, Bacteroidia, and Beta- and Gamma-proteobacteria. Psychological distress was also associated with decreases in operational taxonomic units from the lineages of Lachnospiraceae, Fusobacteriaceae, Ruminococcaceae, Veillonellaceae, Alcaligenaceae, Desulfovibrionaceae, and Bacteroidaceae families. The relative abundance of Bifidobacterium in patients with Crohn’s disease and Desulfovibrio in patients with ulcerative colitis correlated with depression, whereas abundance of Sutterella, RF 32, and Lactococcus correlated with quality of life in patients with Crohn’s disease.
We identified correlations between the composition of the intestinal microbiota in patients with IBD and remission, psychological well-being, and QoL. Further studies should investigate how intestinal inflammation, the microbiome, and microbial metabolites affect psychological well-being and whether these components are mono- or bi-directionally linked.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
Bacteria; CD; Gut–Brain Interactions; Psychology
The authors used patients from the Swiss Inflammatory Bowel Disease Cohort to examine relationship between intestinal microbiota and well-being via self-report scales for patients in remission. Patients with increased perceived stress, moderate to high scores of anxiety, and moderate to high scores of depression were all found to have decreased microbial species richness.
Strength and weaknesses:
Strengths include direct measurement of microbacterium via biopsy versus fecal levels, the strict inclusion of patients only in remission, and already established cohort undergoing regular standardized administration of tests. Weaknesses include inability to determine directionality of the findings due to study design and possible confounding variables of patients within cohort being more involved in regular medical care and highly motivated versus IBD patients not participating in study.
This study adds to evidence that intestinal microbiota of IBD patients are altered, even in remission, and serves to further demonstrate an association with patient- perceived quality of life, anxiety, and depression. This highlights the importance of psychiatric conditions in IBD patients and the need for focus on psychological well-being during all states of the disease.
Type of study:
(http://ebm.bmj.com/content/early/2016/06/23/ebmed-2016-110401): nationwide database prospective cohort
PUBLICATION #3 — GI Psychiatry
Psychiatric medication use and weight outcomes one year after bariatric surgery.
Hawkins M, Leung SE, Lee A, Wnuk S, Cassin S, Hawa R, Sockalingam S.
Given the high rates of psychiatric comorbidity in bariatric surgery patients, pharmacotherapy is common and could potentially influence weight loss outcomes.
We aimed to identify the impact of psychotropic medication use on percent total weight loss (%TWL) 1 year after bariatric surgery.
In this prospective cohort study, 190 patients were compared based on demographic variables (age, sex, relationship status, employment status), body mass index, %TWL, and psychotropic medication use before and 1 year after bariatric surgery. An analysis of variance test was used as a global test of significance for psychotropic medication comparisons related to %TWL. Significance of post hoc comparisons was calculated with the Tukey’s Honestly Significance Difference test.
Sixty-one of 190 (32.1%) patients were taking psychiatric medications before surgery; of those, 82% (50/61) continued to take psychiatric medications 1-year after surgery. %TWL did not significantly differ between patients taking no psychiatric medications, one medication, or more than one medication 1 year after surgery (31.4% vs. 29.9% vs. 34.4%, respectively). Among patients taking antidepressants, those taking serotonin-norepinephrine reuptake inhibitors had a significantly higher %TWL than those taking selective serotonin reuptake inhibitors (36.4% vs. 27.8%; P = 0.032).
This longitudinal study suggests that psychiatric medication use was not associated with poorer %TWL at 1 year after bariatric surgery. Within class, antidepressant use may have differential effects on weight loss after bariatric surgery and warrants further investigation.
Copyright © 2019 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.
bariatric surgery; medication; obesity; psychotropic
In this study, 175 patients received Roux-en-Y gastric bypass while 15 received sleeve gastrectomy. Of the 61 patients taking a psychiatric medication before surgery, 50 were still taking medication 1 year after surgery. The most common classes of psychiatric medications were antidepressants and benzodiazepines. When comparing patients taking no medications, SSRI’s, and SNRI’s 1 year after surgery, there was a significant difference in mean %TWL between the different groups. Patients taking SNRI’s had a higher %TWL when compared to those taking SNRI’s.
Strength and weaknesses:
The patient sample was a subset of the Toronto Bariatric Surgery Psychosocial cohort study and all participants received Roux-en-Y gastric bypass surgery unless a gastric sleeve was indicated. When looking at patients taking medication classes other than antidepressants and benzodiazepines, the number was small. Therefore, the study lacked power to detect differences between medication classes and weight loss outcomes. Additionally, data was not gathered on lifestyle factors such as diet and exercise before and after surgery, so it is unclear how results may been affected by this lack of information.
Previous studies have shown an association between obesity and mental health conditions including mood, anxiety, and alcohol use disorders. Unsurprisingly, many individuals seeking bariatric surgery are on one or more psychotropic medications, especially antidepressants. Multiple bariatric procedures exist and more recent studies have focused on patients who had Roux-en-Y gastric bypass surgery. Data is unfortunately sparse on the exact pharmacokinetic changes associated with bariatric surgery in those taking psychotropics. While certain antidepressants are more closely associated with weight gain, future research should look at the mechanisms that explain why a difference in %TWL exists in patients taking different classes of medications.
Type of study: