scholarly journals Gut Microbial Dysbiosis is Correlated with Stroke Severity Markers in Aged Rats Following Stroke

2021 ◽  
Author(s):  
Tyler C. Hammond ◽  
Sarah Messmer ◽  
Jaqueline A. Frank ◽  
Douglas Lukins ◽  
Rita Colwell ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Inflammatory Markers ◽  
Species Level ◽  
Fold Change ◽  
Female Rats ◽  
Stroke Severity ◽  
Aged Rats ◽  
Ruminococcus Flavefaciens ◽  
Akkermansia Muciniphila ◽  
Lactobacillus Murinus

Abstract Background: An imbalanced gut microbial community, or dysbiosis, has been shown to occur following stroke. It is possible that this dysbiosis negatively impacts stroke recovery and rehabilitation. Species level resolution measurements of the gut microbiome following stroke are needed to develop and test precision interventions such as probiotic or fecal microbiota transplant therapies that target the gut microbiome following stroke. Previous studies have used 16S rRNA amplicon sequencing in young male mice to obtain broad profiling of the gut microbiome at the genus level following stroke, but further investigations will be needed with whole genome shotgun sequencing in aged rats of both sexes to obtain species level resolution in a model which will better translate to the demographics of human stroke patients.Results: 39 aged male and female rats underwent middle cerebral artery occlusion. Fecal samples were collected before stroke and three days post stroke to measure gut microbiome. Machine learning was used to identify the top ranked bacteria which were changed following stroke. MRI imaging was used to obtain infarct and edema size and cerebral blood flow (CBF). ELISA was used to obtain inflammatory markers. Dysbiosis was demonstrated by an increase in pathogenic bacteria such as Butyricimonas virosa (15.52 fold change, p<0.0001), Bacteroides vulgatus (7.36 fold change, p<0.0001), and Escherichia coli (47.67 fold change, p<0.0001). These bacteria were positively associated with infarct and edema size and with the inflammatory markers Ccl19, Ccl24, IL17a, IL3, and complement C5; they were negatively correlated with CBF. Conversely, beneficial bacteria such as Ruminococcus flavefaciens (0.14 fold change, p<0.0001), Akkermansia muciniphila (0.78 fold change, p<0.0001), and Lactobacillus murinus (0.40 fold change, p<0.0001) were decreased following stroke and associated with all the previous parameters in the opposite direction of the pathogenic species. There were not significant microbiome differences between the sexes.Conclusion: The species level resolution measurements found here can be used as a foundation to develop and test precision interventions targeting the gut microbiome following stroke. Probiotics that include Ruminococcus flavefaciens, Akkermansia muciniphila, and Lactobacillus murinus should be developed to target the deficit following stroke to measure the impact on stroke severity.

scholarly journals Fecal microbiota transplantation mitigates bone loss by improving gut microbiome composition and gut barrier function in aged rats

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12293
Author(s):  
Sicong Ma ◽  
Ning Wang ◽  
Pu Zhang ◽  
Wen Wu ◽  
Lingjie Fu
Keyword(s):  
Bone Loss ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Bone Volume ◽  
Female Rats ◽  
Control Group ◽  
Aged Rats ◽  
Senile Osteoporosis ◽  
Microbiome Composition

Background Gut microbiota (GM) dysbiosis is closely related to bone loss and the occurrence of osteoporosis in animals and human. However, little is known about the effect and the mechanisms of fecal microbiota transplantation (FMT) on bone in the treatment of senile osteoporosis. Methods Aged female rats were randomly divided into the FMT group and the control group. 3-month-old female rats were used as fecal donors. The rats were sacrificed at 12 and 24 weeks following transplantation and the serum, intestine, bone, and feces were collected for subsequent analyses. Results The bone turnover markers of osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), and carboxy-terminal peptide (CTX) decreased significantly at 12 and 24 weeks following FMT (P < 0.05). At 12 weeks following transplantation, histomorphometric parameters including the bone volume (BV), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) of the FMT group were comparable to the control group. However, at 24 weeks following transplantation, these parameters of the FMT group were significantly higher than those of the control group (P < 0.05). Besides, the GM aggregated at 12 and 24 weeks following FMT, and the ecological distance was close between the rats in the FMT group and the donor rats. Alpha diversity, shown by the Shannon index and Simpson index, and the Firmicutes/Bacteroidetes ratio decreased significantly after FMT at 24 weeks. Furthermore, FMT restored the GM composition in aged rats at the phylum and family level, and the intestinal microbiota of the aged rats was similar to that of the donor rats. Correlation network analysis indirectly suggested the causality of FMT on alleviating osteoporosis. FMT improved the intestinal structure and up-regulated the expression of tight junction proteins of occludin, claudin, and ZO-1, which might be associated with the protective effects of FMT on bone. Conclusions GM transplanted from young rats alleviated bone loss in aged rats with senile osteoporosis by improving gut microbiome composition and intestinal barrier function. These data might provide a scientific basis for future clinical treatment of osteoporosis through FMT.

scholarly journals Comparative Genomics Guides Elucidation of Vitamin B12 Biosynthesis in Novel Human-Associated Akkermansia Strains

2019 ◽  
Vol 86 (3) ◽  
Author(s):  
Nina Kirmiz ◽  
Kadir Galindo ◽  
Karissa L. Cross ◽  
Estefani Luna ◽  
Nicholas Rhoades ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Species Level ◽  
Vitamin B ◽  
Human Gut ◽  
Content Type ◽  
Human Host ◽  
Akkermansia Muciniphila ◽  
Human Gut Microbiome ◽  
Physiological Diversity ◽  
Bacterial Lineage

ABSTRACT Akkermansia muciniphila is a mucin-degrading bacterium found in the gut of most humans and is considered a “next-generation probiotic.” However, knowledge of the genomic and physiological diversity of human-associated Akkermansia sp. strains is limited. Here, we reconstructed 35 metagenome-assembled genomes and combined them with 40 publicly available genomes for comparative genomic analysis. We identified at least four species-level phylogroups (AmI to AmIV), with distinct functional potentials. Most notably, we identified genes for cobalamin (vitamin B12) biosynthesis within the AmII and AmIII phylogroups. To verify these predictions, 10 Akkermansia strains were isolated from adults and screened for vitamin B12 biosynthesis genes via PCR. Two AmII strains were positive for the presence of cobalamin biosynthesis genes, while all 9 AmI strains tested were negative. To demonstrate vitamin B12 biosynthesis, we measured the production of acetate, succinate, and propionate in the presence and absence of vitamin supplementation in representative strains of the AmI and AmII phylogroups, since cobalamin is an essential cofactor in propionate metabolism. Results showed that the AmII strain produced acetate and propionate in the absence of supplementation, which is indicative of vitamin B12 biosynthesis. In contrast, acetate and succinate were the main fermentation products for the AmI strains when vitamin B12 was not supplied in the culture medium. Lastly, two bioassays were used to confirm vitamin B12 production by the AmII phylogroup. This novel physiological trait of human-associated Akkermansia strains may affect how these bacteria interact with the human host and other members of the human gut microbiome. IMPORTANCE There is significant interest in the therapeutic and probiotic potential of the common gut bacterium Akkermansia muciniphila. However, knowledge of both the genomic and physiological diversity of this bacterial lineage is limited. Using a combination of genomic, molecular biological, and traditional microbiological approaches, we identified at least four species-level phylogroups with differing functional potentials that affect how these bacteria interact with both their human host and other members of the human gut microbiome. Specifically, we identified and isolated Akkermansia strains that were able to synthesize vitamin B12. The ability to synthesize this important cofactor broadens the physiological capabilities of human-associated Akkermansia strains, fundamentally altering our understanding of how this important bacterial lineage may affect human health.

scholarly journals Acute pre-operative ibuprofen improves cognition in a rat model for postoperative cognitive dysfunction

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Klaske Oberman ◽  
Iris Hovens ◽  
Jacco de Haan ◽  
Joana Falcao-Salles ◽  
Barbara van Leeuwen ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Morris Water Maze ◽  
Rat Model ◽  
Gut Microbiome ◽  
Water Maze ◽  
Single Injection ◽  
Postoperative Cognitive Dysfunction ◽  
Aged Rats ◽  
Short Term ◽  
Term Memory

Abstract Background Inflammation is considered a key factor in the development of postoperative cognitive dysfunction (POCD). Therefore, we hypothesized that pre-operative anti-inflammatory treatment with ibuprofen would inhibit POCD in our rat-model. Methods Male Wistar rats of 3 or 23 months old received a single injection of ibuprofen (15 mg/kg i.p.) or were control handled before abdominal surgery. Timed blood and fecal samples were collected for analyses of inflammation markers and gut microbiome changes. Behavioral testing was performed from 9 to 14 days after surgery, in the open field, novel object- and novel location-recognition tests and Morris water maze. Neuroinflammation and neurogenesis were assessed by immune histochemistry after sacrifice on postoperative day 14. Results Ibuprofen improved short-term spatial memory in the novel location recognition test, and increased hippocampal neurogenesis. However, these effects were associated with increased hippocampal microglia activity. Whereas plasma cytokine levels (IL1-β, IL6, IL10, and TNFα) were not significantly affected, VEGF levels increased and IFABP levels decreased after ibuprofen. Long-term memory in the Morris water maze was not significantly improved by ibuprofen. The gut microbiome was neither significantly affected by surgery nor by ibuprofen treatment. In general, effects in aged rats appeared similar to those in young rats, though less pronounced. Conclusion A single injection of ibuprofen before surgery improved hippocampus-associated short-term memory after surgery and increased neurogenesis. However, this favorable outcome seemed not attributable to inhibition of (neuro)inflammation. Potential contributions of intestinal and blood-brain barrier integrity need further investigation. Although less pronounced compared to young rats, effects in aged rats indicate that even elderly individuals could benefit from ibuprofen treatment.

PLASMA PROLACTIN AND PROGESTERONE RESPONSES TO MATING ARE ALTERED IN AGED RATS

1981 ◽  
Vol 90 (2) ◽  
pp. 179-191 ◽  
Author(s):  
S. HENDRICKS ◽  
C. A. BLAKE
Keyword(s):  
Plasma Concentrations ◽  
External Jugular Vein ◽  
Female Rats ◽  
Plasma Prolactin ◽  
Aged Rats ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Plasma Progesterone ◽  
The One ◽  
The Right

The effects of varying amounts of copulatory stimulation on patterns of plasma concentrations of prolactin and progesterone were evaluated in 3- and 12-month-old female rats. The 12-month-old group included rats which still exhibited oestrous cycles and rats in persistent vaginal oestrus (PVO). The extent of copulatory stimulation was defined by the number of intromissions received during mating: ≤5,15 or > 50. Blood samples were drawn over the 8 days after mating through a cannula inserted into the right external jugular vein. Plasma from the samples was assayed for prolactin and progesterone. In aged but still cyclic rats, pregnancy rates were positively correlated with the number of intromissions received during mating. Only one rat in PVO became pregnant. All animals which became pregnant and rats in PVO which, after mating, exhibited a disruption of the pattern of PVO, showed the nocturnal surge of plasma prolactin characteristic of pregnant and pseudopregnant rats. While these surges persisted until day 8 after mating in pregnant animals, they were absent by this time in the rats in PVO. Prolactin surges were present in some but not all of the aged rats which did not become pregnant. Progesterone concentrations were raised in all pregnant animals except the one pregnant rat in PVO and, while not related to the number of intromissions, concentrations were higher 8 days after mating in young compared with those in aged pregnant rats. Plasma progesterone was low in rats in PVO regardless of disruption of the pattern of PVO. We have concluded that the failure of limited copulatory stimulation to induce pregnancy in older rats results, at least in part, from its failure to initiate nocturnal prolactin surges. Nevertheless, our data suggest that matings which are not experimentally limited should provide ample stimulation to establish such surges. Although reduced plasma concentrations of prolactin and progesterone at pro-oestrus and reduced plasma progesterone through part of gestation may contribute to decreasing fertility in aged rats, other unidentified factors appear to be involved in mediating the capacity of extensive copulatory stimulation to induce pregnancy in these animals.

scholarly journals Age-Related Effects on Right Femoral Bone of Male Wistar Rats: A Morphometric and Biomechanical Study

2021 ◽  
Author(s):  
Sheila Martins Puelker ◽  
Sonia Regina Ribeiro de Castro ◽  
Romeu Rodrigues de Souza ◽  
Laura Beatriz Mesiano Maifrino ◽  
Ricardo Aparecido Baptista Nucci ◽  
...  
Keyword(s):  
Cortical Thickness ◽  
Wistar Rats ◽  
Female Rats ◽  
Male Rats ◽  
Aged Rats ◽  
Femoral Bone ◽  
Middle Aged ◽  
Left Femur ◽  
Bone Stiffness ◽  
The Right

Abstract Introduction Study of the variations of bone characteristics with age in different animal models is important to design musculoskeletal studies. Thus, this study aimed to evaluate the bone mass, dimensions, and biomechanical parameters of the femur in young, middle-aged, and aged Wistar rats. Materials and Methods Thirty male rats (Rattus norvegicus) were divided in three groups (n = 10 per group)—3-month-old young rats, 12-month-old middle-aged rats, and 18-months-old aged rats. The right femurs were subjected sequentially to morphometric study (bone weight, cortical thickness) and biomechanical tests (maximum resistance strength and bone stiffness). Results We observed a significant increase in femur histological (cortical thickness) and biomechanical (maximum strength and bone stiffness) parameters with aging when compared with young animals. Conclusions With the advancing age, the right femoral bone of middle-aged and old animals had greater variations when compared with young animals. However, further studies with the aid of a comparison between right and left femur and other long bones in both male and female rats are needed to corroborate with our findings.

Glutamine synthetase induction by glucocorticoids is preserved in skeletal muscle of aged rats

1996 ◽  
Vol 271 (6) ◽  
pp. E1061-E1066 ◽  
Author(s):  
D. Meynial-Denis ◽  
M. Mignon ◽  
A. Miri ◽  
J. Imbert ◽  
E. Aurousseau ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glutamine Synthetase ◽  
Skeletal Muscles ◽  
Female Rats ◽  
Mrna Levels ◽  
Aged Rats ◽  
Adult Rats ◽  
Adult Age ◽  
Slow Twitch ◽  
Fast Twitch

Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid induction of GS could be altered in aged rats, because alterations in the responsiveness of some genes to glucocorticoids were reported in aging. We compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6-8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex) in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and aged rat, respectively) for 5 days. Dex caused an increase in both GS activity and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged rats. In contrast, Dex increased GS activity in heart of adult rats, without any concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is preserved in skeletal muscle but not in heart from aged animals.

scholarly journals Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial

Gut ◽  
2017 ◽  
Vol 68 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Henrik Munch Roager ◽  
Josef K Vogt ◽  
Mette Kristensen ◽  
Lea Benedicte S Hansen ◽  
Sabine Ibrügger ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Sensitivity ◽  
Gut Microbiome ◽  
Inflammatory Markers ◽  
Dietary Intervention ◽  
Short Chain Fatty Acids ◽  
Low Grade ◽  
Whole Grain ◽  
Intestinal Transit Time ◽  
Low Grade Inflammation

ObjectiveTo investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality.Design60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed.Results50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye.ConclusionCompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation.Trial registration numberNCT01731366; Results.

Relation of attenuated proestrous luteinizing hormone surges in middle-aged female rats to in vitro pituitary gonadotropin-releasing hormone responsiveness

1994 ◽  
Vol 130 (5) ◽  
pp. 540-544 ◽  
Author(s):  
Aurelia N Brito ◽  
Timothy E Sayles ◽  
Richard J Krieg ◽  
Dennis W Matt
Keyword(s):  
Luteinizing Hormone ◽  
Gonadotropin Releasing Hormone ◽  
Female Rats ◽  
Aged Rats ◽  
Middle Aged ◽  
Releasing Hormone ◽  
Young Females ◽  
Pituitary Gonadotropin ◽  
Hormone Responsiveness

Brito AN, Sayles TE, Krieg Jr RJ, Matt DW. Relation of attenuated proestrous luteinizing hormone surges in middle-aged female rats to in vitro pituitary gonadotropin-releasing hormone responsiveness. Eur J Endocrinol 1994;130:540–4. ISSN 0804–4643 Prior to the cessation of regular cyclicity, middle-aged rats display pre-ovulatory luteinizing hormone (LH) surges of reduced magnitude. The present study was designed to identify whether middle-aged female rats with attenuated proestrous LH surges have alterations in pituitary responsiveness to gonadotropin-releasing hormone (GnRH). Young (4 months old) and middle-aged (10–12 months old) regularly cycling females were catheterized and sampled on proestrus to characterize their LH surge profiles. On the next proestrus (12.00 h), pituitaries were perifused individually and exposed to three pulses of GnRH (30 nmol/l). The patterns of the proestrous LH surges revealed that 12 of 22 middle-aged rats had attenuated surges (< 7 μg/l) while the remaining 10 middle-aged females had surges that were similar to those of young rats. Pituitaries perifused on the next proestrus showed similar basal LH release among the middle-aged and young females. However, the LH secretory rates following the second and third administration of GnRH, as well as the overall GnRH-stimulated LH secretory rates, were significantly decreased in middle-aged females with previously attenuated LH surges as compared to those from the young proestrous rats. In contrast, middle-aged rats with normal LH surges had pituitary LH responses that were no different from those of young females. These results indicate that a decrease in pituitary LH responsiveness to GnRH is only apparent in middle-aged rats that display attenuated proestrous LH surges. Dennis W Matt. Department of Obstetrics and Gynecology, Medical College of Virginia, Box 980034, Richmond, VA 23298, USA

scholarly journals Multi-omics examination of Q fever fatigue syndrome identifies similarities with chronic fatigue syndrome

2020 ◽  
Author(s):  
Ruud Raijmakers ◽  
Megan E. Roerink ◽  
Anne F.M. Jansen ◽  
Stephan P. Keijmel ◽  
Ranko Gacesa ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Gut Microbiome ◽  
Inflammatory Markers ◽  
Molecular Mechanisms ◽  
Q Fever ◽  
Chronic Fatigue ◽  
Metagenomic Sequencing ◽  
Illumina Hiseq ◽  
Fatigue Syndrome ◽  
Q Fever Fatigue Syndrome

Abstract Background: Q fever fatigue syndrome (QFS) is characterised by a state of prolonged fatigue that is seen in 20% of acute Q fever infections and has major health-related consequences. The molecular mechanisms underlying QFS are largely unclear. In order to better understand its pathogenesis, we applied a multi-omics approach to study the patterns of the gut microbiome, blood metabolome, and inflammatory proteome of QFS patients, and compared these with those of chronic fatigue syndrome (CFS) patients and healthy controls (HC). Methods: The study population consisted of 31 QFS patients, 50 CFS patients, and 72 HC. All subjects were matched for age, gender, and general geographical region (South-East part of the Netherlands). The gut microbiome composition was assessed by Metagenomic sequencing using the Illumina HiSeq platform. A total of 92 circulating inflammatory markers were measured using Proximity Extension Essay and 1607 metabolic features were assessed with a high-throughput non-targeted metabolomics approach. Results: Inflammatory markers, including 4E-BP1 (P = 9.60-16 and 1.41-7) and MMP-1 (P = 7.09-9 and 3.51-9), are significantly more expressed in both QFS and CFS patients compared to HC. Blood metabolite profiles show significant differences when comparing QFS (319 metabolites) and CFS (441 metabolites) patients to HC, and are significantly enriched in pathways like sphingolipid (P = 0.0256 and 0.0033) metabolism. When comparing QFS to CFS patients, almost no significant differences in metabolome were found. Comparison of microbiome taxonomy of QFS and CFS patients with that of HC, shows both in- and decreases in abundancies in Bacteroidetes (with emphasis on Bacteroides and Alistiples spp.), and Firmicutes and Actinobacteria (with emphasis on Ruminococcus and Bifidobacterium spp.). When we compare QFS patients to CFS patients, there is a striking resemblance and hardly any significant differences in microbiome taxonomy are found.Conclusions: We show that QFS and CFS patients are similar across three different omics layers and 4E-BP1 and MMP-1 have the potential to distinguish QFS and CFS patients from HC.

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