scholarly journals A50 TRANSFER OF DEPRESSIVE-LIKE PHENOTYPE TO GNOTOBIOTIC MICE DEPENDS ON MICROBIAL FEATURES SPECIFIC TO INDIVIDUAL PATIENTS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 59-60
Author(s):  
J Hanuschak ◽  
M P Louis-Auguste ◽  
G De Palma ◽  
E Verdu ◽  
R Anglin ◽  
...  

Abstract Background Major depressive disorder (MDD) affects approximately 4.4% of the global population. Despite its high prevalence, little is known about the mechanisms underlying this disorder. Recent studies in both humans and rodents have suggested that the intestinal microbiota may play a role in depression. Altered microbiota composition has been found in a subset of MDD patients. Preclinical studies have suggested that fecal microbiota transplant using pooled MDD patient samples can induce depressive-like behaviour in rodents. We have previously shown that the use of different microbiota donors with irritable bowel syndrome results in the induction of different phenotypes in recipient mice. Thus, we have hypothesized that pooling microbiota samples abrogates features that are unique to individual donors. Aims (1) Investigate whether the transfer of individual MDD patient microbiota can induce depressive-like behaviour in germ-free (GF) mice (2) Identify features of individual MDD patient microbiota that are associated with the depressive-like phenotype Methods GF NIH Swiss mice of both sexes (min. n=10 per group, total n=110) were colonized with either fecal microbiota from a single donor, MDD patient (MDD1-4) or matched healthy control (HC1-4), or pooled fecal microbiota from MDD1-4 or HC1-4. Mouse behaviour was assessed, using the open field test, three chamber sociability assay, tail suspension test, and sucrose preference test. Stool samples were collected throughout the experiment for 16S rRNA gene sequencing. Results Mice colonized with microbiota from patient MDD1 exhibited depressive-like behaviour, as assessed by the sucrose preference test and sociability assay, when compared to mice colonized with HC1 microbiota. This was not true for mice colonized with individual microbiota from the other three patients (MDD2-4) or with pooled MDD microbiota. Comparative analysis of the 16S data revealed a significant difference in Faith’s Phylogenetic Diversity between MDD1 microbiota and pooled MDD microbiota. Four bacterial species were found to be significantly associated with the depressive-like phenotype in mice: Bacteroides acidifaciens, Bacteroides ovatus, unclassified species of Phascolarctobacterium (Veillonellacae family), and Eggerthella lenta. The relative abundances of these species did not differ significantly between the two pooled groups. Conclusions Microbiota from some, but not all, MDD patients can induce a depressive-like phenotype in GF mice. The ability to induce depressive-like behaviour in GF mice is lost when microbiota from multiple patients is pooled. Specific bacterial species may be responsible for the successful transfer of the depressive-like phenotype to mice. Funding Agencies NIH

Author(s):  
DINESH DHINGRA ◽  
SUDHA

Objectives: The present study was undertaken to investigate the antidepressant potential of trans-anethole in unstressed and stressed male mice. Methods: Swiss albino male mice were exposed to chronic unpredictable mild stress for 21 successive days. Simultaneously, trans-anethole (12.5 mg/kg, 25 mg/kg, and 50 mg/kg) and fluoxetine (20 mg/kg) per se were administered for 21 successive days to separate groups of unstressed and stressed mice. The effect of drugs on depressive-like behavior of mice was tested by tail suspension test (TST) and sucrose preference test. Results: Trans-anethole (25 mg/kg) and fluoxetine significantly decreased the immobility period of unstressed and stressed mice in TST as compared to their respective control. These drugs significantly restored the reduced sucrose preference (%) in stressed mice. Trans-anethole did not show any significant effect on locomotor activity of mice. Antidepressant-like activity of trans-anethole (25 mg/kg) was found to be comparable to fluoxetine. Trans-anethole and fluoxetine significantly inhibited brain monoamine oxidase-A (MAO-A) activity, decreased plasma nitrite, brain malondialdehyde, and increased brain reduced glutathione levels and catalase activity in unstressed and stressed mice. The drugs significantly reversed stress-induced increase in plasma corticosterone levels. Conclusion: Trans-anethole produced significant antidepressant-like activity in unstressed and stressed mice, possibly through inhibition of brain MAO-A activity and alleviation of oxidative stress. Reversal of stress-induced increase in plasma corticosterone levels might also be responsible for antidepressant-like activity of trans-anethole in stressed mice.


2021 ◽  
Vol 15 ◽  
Author(s):  
Weinan Zhao ◽  
Qing Li ◽  
Yu Ma ◽  
Zhiyong Wang ◽  
Bingqian Fan ◽  
...  

Robust sex difference among humans regarding psychiatry- and pain-related behaviors is being researched; however, the use of female mice in preclinical research is relatively rare due to an unchecked potential behavioral variation over the estrous cycle. In the present study, a battery of psychiatry- and pain-related behaviors are examined under physiological condition in female C57BL/6J mice over different estrous cycle phases: proestrus, estrous, metestrous, diestrous. Our behavioral results reveal that there is no significant difference over different phases of the estrous cycle in social interaction test, sucrose preference test, tail suspension test, open field test, marble burying test, novelty-suppressed feeding test, Hargreaves thermal pain test, and Von Frey mechanical pain test. These findings implicate those psychiatry- and pain-related behaviors in normal female C57BL/6J mice appear to be relatively consistent throughout the estrous cycle; the estrous cycle might not be a main contributor to female C57BL/6J mice’s variability of behaviors.


Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 748 ◽  
Author(s):  
Jin-Young Lee ◽  
Mohamed Mannaa ◽  
Yunkyung Kim ◽  
Jehun Kim ◽  
Geun-Tae Kim ◽  
...  

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.


2011 ◽  
Vol 115 (4) ◽  
pp. 812-821 ◽  
Author(s):  
Jing Wang ◽  
Yossef Goffer ◽  
Duo Xu ◽  
David S. Tukey ◽  
D. B. Shamir ◽  
...  

Background Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its antinociceptive properties. Methods The authors examined whether the spared nerve injury model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats spared nerve injury-induced depression. Results Spared nerve injury-treated rats, compared with control rats, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10 mg/kg) did not alter spared nerve injury-induced hypersensitivity; however, it treated spared nerve injury-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control rats 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control rats 5 days after administration). Conclusions Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain.


2013 ◽  
Vol 80 (2) ◽  
pp. 478-485 ◽  
Author(s):  
Yue Tang ◽  
Anthony Underwood ◽  
Adriana Gielbert ◽  
Martin J. Woodward ◽  
Liljana Petrovska

ABSTRACTThe animal gastrointestinal tract houses a large microbial community, the gut microbiota, that confers many benefits to its host, such as protection from pathogens and provision of essential metabolites. Metagenomic approaches have defined the chicken fecal microbiota in other studies, but here, we wished to assess the correlation between the metagenome and the bacterial proteome in order to better understand the healthy chicken gut microbiota. Here, we performed high-throughput sequencing of 16S rRNA gene amplicons and metaproteomics analysis of fecal samples to determine microbial gut composition and protein expression. 16 rRNA gene sequencing analysis identifiedClostridiales,Bacteroidaceae, andLactobacillaceaespecies as the most abundant species in the gut. For metaproteomics analysis, peptides were generated by using the Fasp method and subsequently fractionated by strong anion exchanges. Metaproteomics analysis identified 3,673 proteins. Among the most frequently identified proteins, 380 proteins belonged toLactobacillusspp., 155 belonged toClostridiumspp., and 66 belonged toStreptococcusspp. The most frequently identified proteins were heat shock chaperones, including 349 GroEL proteins, from many bacterial species, whereas the most abundant enzymes were pyruvate kinases, as judged by the number of peptides identified per protein (spectral counting). Gene ontology and KEGG pathway analyses revealed the functions and locations of the identified proteins. The findings of both metaproteomics and 16S rRNA sequencing analyses are discussed.


2021 ◽  
Vol 21 (04) ◽  
pp. 17854-17875
Author(s):  
Edda Lungu ◽  
◽  
J Auger ◽  
A Piano ◽  
WJ Dahl ◽  
...  

Dietary fiber favorably modulates gut microbiota and may be protective against diarrhea in sub-Saharan Africa where rates in infants and young children are high. Soybean hull is high in fiber and accessible in rural Africa; however, its use in complementary feeding has not been evaluated. The objective of this study was to determine the acceptability and feasibility of a soybean, soy hull fiber, and maize (SFM) blend food; the primary outcome was compliance to the feeding protocol. Secondary outcomes were stool form and frequency, fecal microbiota composition, growth and dietary intake. In a parallel, single-blind study, children 6-36 months of age from the Lilongwe district of Malawi were randomized to receive daily SFM (n=69) or maize only(n=10) porridge(phala) for 6 months. Anthropometrics were measured monthly, and compliance, stool frequency,and stool form, weekly. At baseline, 3-month,and 6-month (study end) time points, dietary intake (24-h recall) was assessed,and fecal samples were collected. Fecal DNA was analyzed by Real-Time polymerase chain reaction (PCR) for microbes of interest and 16S rRNA gene amplicon sequencing. Mothers accessed the acceptability and feasibility of the study foods at study end. Mothers reported excellent compliance to feeding the SFM porridge, rated it more acceptable than maize,and noted improved appetite, weight, and stool consistency of their children. Stool frequency at baseline (2±1 stools/d) was unchanged with intervention; however, there were significantly fewer diarrhea-type stools reported during study months 4-6 vs.1-3 for the SFM group, whereas no improvement was seen for the maize group. At study end, the fecal abundance ofAkkermansia muciniphila was enriched in children receiving the SFM, compared to maize (p<0.05), and a trend for increased Faecalibacterium prausnitzii (p=0.07) was seen. A comparison of fecal microbiota composition using linear discriminant analysis effect size (LEfSe)showed notable differences in numerous taxa in the SFM group compared to baseline, whereas the maize comparator exhibited fewer changes. Fiber intake was higher for the SFMgroup, compared to maize at 6 months (13.7±3.8 vs. 8.4±4.5 g/day, p<0.01). Weight-for-height and BMI-for-age Z-scores were significantly higher for the SFM group. In young Malawian children, feeding a blend of soybean, soy hulls and maize reduced diarrhea-type stools and increased the abundance of Akkermansia muciniphila, a bacterial species involved in maintaining intestinal health, and thus may provide a feasible means of improving wellness in children in resource-poor settings through the modulation of microbiota composition.


Author(s):  
Naomi N Lee ◽  
Willie A Bidot ◽  
Aaron C Ericsson ◽  
Craig L Franklin

The gut microbiota (GM) is the sum of hundreds of distinct microbial species that can equal or outnumber their host’ssomatic cells. The GM influences a multitude of physiologic and immunologic processes in the host, and changes in the GM have been shown to alter the phenotypes of animal models. Previous studies using rodents have also shown that the composition of the GM is affected by many factors, including diet, husbandry, housing, and the genetic background of the animals. However, limited information exists about factors that may modulate GM in other laboratory species, such as dogs. We sought to eliminate sporadic Giardia colonization of dogs using fenbendazole (FBZ), an antiprotozoal widely used in biomedical research dog colonies. Concerns that FBZ could have inadvertent effects on the canine GM led us to assess GM over the course of treatment. FBZ (50 mg/kg) was given orally to all dogs in 3 different facilities (n = 19 to 25) for 10 consecutive days. Fecal samples were obtained 2 d before the initiation of treatment, on the last day of treatment, and 2 wk after the completion of treatment. Targeted 16S rRNA gene sequencing was used to analyze fecal microbiota. All dogs were clinically normal throughout the sample collection period. Statistical analyses of data showed significant differences between dogs housed in the 3 different facilities, further emphasizing the effect of housing and husbandry factors on the GM. However,negligible differences were seen between time points, indicating that FBZ did not significantly alter the canine GM. Comparison of the GM of Giardia lamblia positive and negative dogs revealed no significant difference between the 2 groups. These findings suggest that FBZ can be used therapeutically in dogs with minimal impact on the GM. Furthermore, the presence ofG. lamblia in clinically normal animals may not be sufficient to influence the normal canine microbiota.


2018 ◽  
Vol 13 (7) ◽  
pp. 1686-1698 ◽  
Author(s):  
Meng-Ying Liu ◽  
Chun-Yu Yin ◽  
Li-Juan Zhu ◽  
Xian-Hui Zhu ◽  
Chu Xu ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document