Sex-dependent Gut Microbiota-brain-cognition Associations: A Multimodal MRI Study

Abstract Background: There is bidirectional communication between the gut microbiota and the brain. Empirical evidence has demonstrated sex differences in both the gut microbiome and the brain. However, the effects of sex on the gut microbiota-brain associations have yet to be determined. Methods: 157 healthy young adults underwent brain structural, perfusion, functional and diffusion MRIs to measure gray matter volume (GMV), cerebral blood flow (CBF), functional connectivity strength (FCS) and white matter integrity, respectively. Fecal samples were collected and 16S rRNA gene amplicon sequencing was utilized to assess gut microbial diversity. Correlation analyses were conducted to test for sex-dependent associations between microbial diversity and brain imaging parameters, and mediation analysis was performed to further characterize the gut microbiota-brain-cognition relationship. Results: We found that higher gut microbial diversity was associated with higher GMV in the right cerebellum Ⅵ, higher CBF in the bilateral calcarine sulcus yet lower CBF in the left superior frontal gyrus, higher FCS in the bilateral paracentral lobule, and lower diffusivity in widespread white matter regions in males. However, these associations were absent in females. Of more importance, these neuroimaging biomarkers significantly mediated the association between gut microbial diversity and behavioral inhibition in males. Conclusions: These findings highlight sex as a potential influential factor underlying the gut microbiota-brain-cognition relationship, and expose the gut microbiota as a biomarker-driven and sex-sensitive intervention target for mental disorders with abnormal behavioral inhibition.

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Ecology impacts the decrease of Spirochaetes and Prevotella in the fecal gut microbiota of urban humans

BMC Microbiology ◽

10.1186/s12866-021-02337-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Louise B. Thingholm ◽

Corinna Bang ◽

Malte C. Rühlemann ◽

Annika Starke ◽

Florian Sicks ◽

...

Keyword(s):

Gut Microbiota ◽

Microbial Diversity ◽

Homo Sapiens ◽

Inflammatory Diseases ◽

General Pattern ◽

Amplicon Sequencing ◽

Controlled Study ◽

Rrna Gene ◽

Microbiota Composition ◽

Host Phylogeny

AbstractCompared to the huge microbial diversity in most mammals, human gut microbiomes have lost diversity while becoming specialized for animal-based diets – especially compared to chimps, their genetically closest ancestors. The lowered microbial diversity within the gut of westernized populations has also been associated with different kinds of chronic inflammatory diseases in humans. To further deepen our knowledge on phylogenetic and ecologic impacts on human health and fitness, we established the herein presented biobank as well as its comprehensive microbiota analysis. In total, 368 stool samples from 38 different animal species, including Homo sapiens, belonging to four diverse mammalian orders were collected at seven different locations and analyzed by 16S rRNA gene amplicon sequencing. Comprehensive data analysis was performed to (i) determine the overall impact of host phylogeny vs. diet, location, and ecology and to (ii) examine the general pattern of fecal bacterial diversity across captive mammals and humans.By using a controlled study design with captive mammals we could verify that host phylogeny is the most dominant driver of mammalian gut microbiota composition. However, the effect of ecology appears to be able to overcome host phylogeny and should therefore be studied in more detail in future studies. Most importantly, our study could observe a remarkable decrease of Spirochaetes and Prevotella in westernized humans and platyrrhines, which is probably not only due to diet, but also to the social behavior and structure in these communities.Our study highlights the importance of phylogenetic relationship and ecology within the evolution of mammalian fecal microbiota composition. Particularly, the observed decrease of Spirochaetes and Prevotella in westernized communities might be associated to lifestyle dependent rapid evolutionary changes, potentially involved in the establishment of dysbiotic microbiomes, which promote the etiology of chronic diseases.

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Effects of Psychotropics on the Microbiome in Patients With Depression and Anxiety: Considerations in a Naturalistic Clinical Setting

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa070 ◽

2020 ◽

Author(s):

Yoshihiro Tomizawa ◽

Shunya Kurokawa ◽

Daiki Ishii ◽

Katsuma Miyaho ◽

Chiharu Ishii ◽

...

Keyword(s):

Gut Microbiota ◽

Microbial Diversity ◽

Depressive Disorders ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Shannon Index ◽

Rrna Gene ◽

Depression And Anxiety ◽

The Impact ◽

Whole Tree

Abstract Background The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. Method We longitudinally investigated the relationship between patients’ prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. Results We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = −0.00254, SE = 0.000595, P < .0001; estimate = −0.02644, SE = 0.00833, P = .002, respectively). Conclusion Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients’ types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.

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Conventional myelosuppressive chemotherapy for non-haematological malignancy disrupts the intestinal microbiome

BMC Cancer ◽

10.1186/s12885-021-08296-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lito E. Papanicolas ◽

Sarah K. Sims ◽

Steven L. Taylor ◽

Sophie J. Miller ◽

Christos S. Karapetis ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Haematological Malignancy ◽

Amplicon Sequencing ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Conventional Chemotherapy ◽

Myelosuppressive Chemotherapy ◽

Gram Positive Bacteria ◽

Faecal Samples

Abstract Background The gut microbiota influences many aspects of host physiology, including immune regulation, and is predictive of outcomes in cancer patients. However, whether conventional myelosuppressive chemotherapy affects the gut microbiota in humans with non-haematological malignancy, independent of antibiotic exposure, is unknown. Methods Faecal samples from 19 participants with non-haematological malignancy, who were receiving conventional chemotherapy regimens but not antibiotics, were examined prior to chemotherapy, 7–12 days after chemotherapy, and at the end of the first cycle of treatment. Gut microbiota diversity and composition was determined by 16S rRNA gene amplicon sequencing. Results Compared to pre-chemotherapy samples, samples collected 7–12 days following chemotherapy exhibited increased richness (mean 120 observed species ± SD 38 vs 134 ± 40; p = 0.007) and diversity (Shannon diversity: mean 6.4 ± 0.43 vs 6.6 ± 0.41; p = 0.02). Composition was significantly altered, with a significant decrease in the relative abundance of gram-positive bacteria in the phylum Firmicutes (pre-chemotherapy median relative abundance [IQR] 0.78 [0.11] vs 0.75 [0.11]; p = 0.003), and an increase in the relative abundance of gram-negative bacteria (Bacteroidetes: median [IQR] 0.16 [0.13] vs 0.21 [0.13]; p = 0.01 and Proteobacteria: 0.015 [0.018] vs 0.03 [0.03]; p = 0.02). Differences in microbiota characteristics from baseline were no longer significant at the end of the chemotherapy cycle. Conclusions Conventional chemotherapy results in significant changes in gut microbiota characteristics during the period of predicted myelosuppression post-chemotherapy. Further study is indicated to link microbiome changes during chemotherapy to clinical outcomes.

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Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Metabolites ◽

10.3390/metabo11080482 ◽

2021 ◽

Vol 11 (8) ◽

pp. 482

Author(s):

Jae-Kwon Jo ◽

Seung-Ho Seo ◽

Seong-Eun Park ◽

Hyun-Woo Kim ◽

Eun-Ju Kim ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

High Fat Diet ◽

Amplicon Sequencing ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

Rrna Gene ◽

High Fat ◽

Underlying Mechanisms ◽

Insight Into

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.

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The microbial community of the gut differs between piglets fed sow milk, milk replacer or bovine colostrum

British Journal Of Nutrition ◽

10.1017/s0007114517000216 ◽

2017 ◽

Vol 117 (7) ◽

pp. 964-978 ◽

Cited By ~ 8

Author(s):

Ann-Sofie R. Poulsen ◽

Nadieh de Jonge ◽

Sugiharto Sugiharto ◽

Jeppe L. Nielsen ◽

Charlotte Lauridsen ◽

...

Keyword(s):

Gut Microbiota ◽

Amplicon Sequencing ◽

Bovine Colostrum ◽

Milk Replacer ◽

Rrna Gene ◽

Bacterial Dna ◽

Faecal Samples ◽

Milk Replacers ◽

The 16S Rrna Gene ◽

Gut Microbiota Composition

AbstractThe aim of this study was to characterise the gut microbiota composition of piglets fed bovine colostrum (BC), milk replacer (MR) or sow milk (SM) in the post-weaning period. Piglets (n36), 23-d old, were randomly allocated to the three diets. Faecal samples were collected at 23, 25, 27 and 30 d of age. Digesta from the stomach, ileum, caecum and mid-colon was collected at 30 d of age. Bacterial DNA from all samples was subjected to amplicon sequencing of the 16S rRNA gene. Bacterial enumerations by culture and SCFA analysis were conducted as well. BC-piglets had the highest abundance ofLactococcusin the stomach (P<0·0001) and ileal (P<0·0001) digesta, whereas SM-piglets had the highest abundance ofLactobacillusin the stomach digesta (P<0·0001). MR-piglets had a high abundance of Enterobacteriaceae in the ileal digesta (P<0·0001) and a higher number of haemolytic bacteria in ileal (P=0·0002) and mid-colon (P=0·001) digesta than SM-piglets. BC-piglets showed the highest colonic concentration of iso-butyric and iso-valeric acid (P=0·02). Sequencing and culture showed that MR-piglets were colonised by a higher number of Enterobacteriaceae, whereas the gut microbiota of BC-piglets was characterised by a change in lactic acid bacteria genera when compared with SM-piglets. We conclude that especially the ileal microbiota of BC-piglets had a closer resemblance to that of SM-piglets in regard to the abundance of potential enteric pathogens than did MR-piglets. The results indicate that BC may be a useful substitute for regular milk replacers, and as a feeding supplement in the immediate post-weaning period.

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Microbial Diversity Profiling of Gut Microbiota of Macropus giganteus Using Three Hypervariable Regions of the Bacterial 16S rRNA

Microorganisms ◽

10.3390/microorganisms9081721 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1721

Author(s):

Christian O’Dea ◽

Roger Huerlimann ◽

Nicole Masters ◽

Anna Kuballa ◽

Cameron Veal ◽

...

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

Microbial Diversity ◽

Surface Waters ◽

Bacterial Species ◽

Rrna Gene ◽

Faecal Contamination ◽

Hypervariable Regions ◽

Geographical Regions ◽

V3 Region

Animal faecal contamination of surface waters poses a human health risk, as they may contain pathogenic bacteria or viruses. Of the numerous animal species residing along surface waterways in Australia, macropod species are a top contributor to wild animals’ faecal pollution load. We characterised the gut microbiota of 30 native Australian Eastern Grey Kangaroos from six geographical regions (five kangaroos from each region) within South East Queensland in order to establish their bacterial diversity and identify potential novel species-specific bacteria for the rapid detection of faecal contamination of surface waters by these animals. Using three hypervariable regions (HVRs) of the 16S rRNA gene (i.e., V1–V3, V3–V4, and V5–V6), for their effectiveness in delineating the gut microbial diversity, faecal samples from each region were pooled and microbial genomic DNA was extracted, sequenced, and analysed. Results indicated that V1-V3 yielded a higher taxa richness due to its larger target region (~480 bp); however, higher levels of unassigned taxa were observed using the V1-V3 region. In contrast, the V3–V4 HVR (~569 bp) attained a higher likelihood of a taxonomic hit identity to the bacterial species level, with a 5-fold decrease in unassigned taxa. There were distinct dissimilarities in beta diversity between the regions, with the V1-V3 region displaying the highest number of unique taxa (n = 42), followed by V3–V4 (n = 11) and V5–V6 (n = 8). Variations in the gut microbial diversity profiles of kangaroos from different regions were also observed, which indicates that environmental factors may impact the microbial development and, thus, the composition of the gut microbiome of these animals.

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The Effects of Chinese Medicine QRD, Antibiotics, and Probiotics on Therapy and Gut Microbiota in Septic Rats

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.712028 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huiling Cao ◽

Chunhui Zong ◽

Wenkui Dai ◽

Qiaoying Gao ◽

Donghua Li ◽

...

Keyword(s):

Chinese Medicine ◽

Gut Microbiota ◽

Survival Rates ◽

Amplicon Sequencing ◽

Medical Emergency ◽

Control Group ◽

Rrna Gene ◽

Sham Operation ◽

Therapeutic Effects

Sepsis is a common and often treacherous medical emergency with a high mortality and long-term complications in survivors. Though antibiotic therapy can reduce death rate of sepsis significantly, it impairs gut microbiota (GM), which play imperative roles in human health. In this study, we compared the therapeutic effects of antibiotics, probiotics, and Chinese medicine QRD on the survival rates of septic model and observed the GM characteristics of experimental rats via 16S rRNA gene amplicon sequencing. The 72 h survival rates of septic rat demonstrated the significant therapeutic effects in the three groups treated with antibiotics (AT), Chinses medicine QRD (QT), and probiotics (PT), which were elevated from the survival rate of 26.67% for the sepsis control group (ST) to 100.0% for AT, 88.24% for QT, and 58.33% for PT. The original characteristics of GM identified in the sham operation controls (SC) were relatively similar to those in PT and QT; nevertheless, the AT rats were shown dramatically decreased in the GM diversity. In addition, the septic rats in AT were revealed the higher abundances of Escherichia Shigella, Proteus, Morganella, Enterococcus, and Lysinibacillus, but the lower those of Parabacteroides, Alistipes, Desulfovibrio, Bacteroides, Helicobacter, Mucispirillum, Oscillibacter, Lachnospiraceae, and Ruminiclostridium 9, when compared to the PT and QT rats. By contrast, the GM of PT and QT rats shared similar diversity and structure. Our findings indicated that QRD increased the survival rates without impairment of the GM characteristics, which provides novel insights into the role of Chinese medicine in therapy and long-term recovery of sepsis.

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Stress-induced anatomical changes in white and gray matter: a review of literature

Medycyna Weterynaryjna ◽

10.21521/mw.6400 ◽

2020 ◽

Vol 76 (06) ◽

pp. 6400-2020

Author(s):

IWONA ŁUSZCZEWSKA-SIERAKOWSKA ◽

KAMIL JONAK

Keyword(s):

White Matter ◽

Gray Matter ◽

Traumatic Event ◽

Gray Matter Volume ◽

Hippocampal Neurogenesis ◽

Anterior Cingulate ◽

Total Brain Volume ◽

Extreme Stress ◽

Mri Morphometry ◽

The Right

Post traumatic stress disorder (PTSD) is a psychiatric abnormality caused by a drastic traumatic event or extreme stress, that exceeds the capability to adapt. There are many papers reporting anatomical brain changes induced by trauma and extreme stress, not only in white matter but in gray matter as well. Extreme stress and trauma are connected with elevation of cortisol level, which may cause damage to the hippocampus and may interfere with the anatomy of the hippocampus as well as its microstructure and cell number. Stress may inhibit the hippocampal neuroregeneration as well as hippocampal neurogenesis and even induce neuronal death within the hippocampus. Diffusor tensor imaging (DTI) is a powerful method enabling the visualization of the microstructure integrity of white matter, to evaluate the changes (rate and directionality) of water diffusion within myelin tracts and provide enhanced images of white matter tracts compared to traditional MRI morphometry images. One can evaluate the differences in white matter using fractional anisotropy (FA), which is a scalar metric of the degree of anisotropy and diffusion direction of water molecules, indicating fiber density, mylination and axon diameter. Many studies report reduced gray matter volume caused by extreme stress or trauma in people both with the diagnosis of PTSD as well as stress-exposed non PTSD in comparison to healthy controls. Studies have revealed reduced volume mostly in the hippocampus but also in regions such as anterior cingulate, corpus callosum, insula, septum pellucidum, subcallosal cortex, amygdala, prefrontal cortex and total brain volume. The right hippocampus may be prone to the effect of stress much more than the left hippocampus. Moreover, comparing trauma-exposed non-PTSD and PTSD participants, they have found volumetric abnormalities only within the right hippocampus among the PTSD group. They suggest an additional pathological process underlying PTSD, connected with the right hippocampus volume.

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Multimodal Magnetic Resonance Imaging reveals alterations of sensorimotor circuits in restless legs syndrome

SLEEP ◽

10.1093/sleep/zsz171 ◽

2019 ◽

Vol 42 (12) ◽

Cited By ~ 3

Author(s):

Ambra Stefani ◽

Thomas Mitterling ◽

Anna Heidbreder ◽

Ruth Steiger ◽

Christian Kremser ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

White Matter ◽

Magnetic Resonance ◽

Gray Matter ◽

Disease Duration ◽

Gray Matter Volume ◽

Resonance Imaging ◽

Iron Storage ◽

Matter Volume ◽

The Right

Abstract Study Objectives Integrated information on brain microstructural integrity and iron storage and its impact on the morphometric profile is not available in restless legs syndrome (RLS). We applied multimodal magnetic resonance imaging (MRI) including diffusion tensor imaging, the transverse relaxation rate (R2*), a marker for iron storage, as well as gray and white matter volume measures to characterize RLS-related MRI signal distribution patterns and to analyze their associations with clinical parameters. Methods Eighty-seven patients with RLS (mean age 51, range 20–72 years; disease duration, mean 13 years, range 1–46 years, of those untreated n = 30) and 87 healthy control subjects, individually matched for age and gender, were investigated with multimodal 3T MRI. Results Volume of the white matter compartment adjacent to the post- and precentral cortex and fractional anisotropy (FA) of the frontopontine tract were both significantly reduced in RLS compared to healthy controls, and these alterations were associated with disease duration (r = 0.25, p = 0.025 and r = 0.23, p = 0.037, respectively). Corresponding gray matter volume increases of the right primary motor cortex in RLS (p < 0.001) were negatively correlated with the right FA signal of the frontopontine tract (r = −0.22; p < 0.05). Iron content evaluated with R2* was reduced in the putamen as well as in temporal and occipital compartments of the RLS cohort compared to the control group (p < 0.01). Conclusions Multimodal MRI identified progressing white matter decline of key somatosensory circuits that may underlie the perception of sensory leg discomfort. Increases of gray matter volume of the premotor cortex are likely to be a consequence of functional neuronal reorganization.

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A core microbiota dominates a rich microbial diversity in the bovine udder and may indicate presence of dysbiosis

Scientific Reports ◽

10.1038/s41598-020-77054-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Davide Porcellato ◽

Roger Meisal ◽

Alberto Bombelli ◽

Judith A. Narvhus

Keyword(s):

Microbial Diversity ◽

Amplicon Sequencing ◽

Rrna Gene ◽

Lactation Period ◽

Strong Negative Correlation ◽

Udder Health ◽

Milk Samples ◽

Lactating Cows ◽

Definition Of ◽

The 16S Rrna Gene

AbstractThe importance of the microbiome for bovine udder health is not well explored and most of the knowledge originates from research on mastitis. Better understanding of the microbial diversity inside the healthy udder of lactating cows might help to reduce mastitis, use of antibiotics and improve animal welfare. In this study, we investigated the microbial diversity of over 400 quarter milk samples from 60 cows sampled from two farms and on two different occasions during the same lactation period. Microbiota analysis was performed using amplicon sequencing of the 16S rRNA gene and over 1000 isolates were identified using MALDI-TOF MS. We detected a high abundance of two bacterial families, Corynebacteriaceae and Staphylococcaceae, which accounted for almost 50% of the udder microbiota of healthy cows and were detected in all the cow udders and in more than 98% of quarter milk samples. A strong negative correlation between these bacterial families was detected indicating a possible competition. The overall composition of the udder microbiota was highly diverse and significantly different between cows and between quarter milk samples from the same cow. Furthermore, we introduced a novel definition of a dysbiotic quarter at individual cow level, by analyzing the milk microbiota, and a high frequency of dysbiotic quarter samples were detected distributed among the farms and the samples. These results emphasize the importance of deepening the studies of the bovine udder microbiome to elucidate its role in udder health.

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