Gut Microbiome, Inflammation, and Cerebrovascular Function: Link Between Obesity and Cognition

Obesity affects 13% of the adult population worldwide and this number is only expected to increase. Obesity is known to have a negative impact on cardiovascular and metabolic health, but it also impacts brain structure and function; it is associated with both gray and white matter integrity loss, as well as decreased cognitive function, including the domains of executive function, memory, inhibition, and language. Especially midlife obesity is associated with both cognitive impairment and an increased risk of developing dementia at later age. However, underlying mechanisms are not yet fully revealed. Here, we review recent literature (published between 2010 and March 2021) and discuss the effects of obesity on brain structure and cognition, with a main focus on the contributions of the gut microbiome, white adipose tissue (WAT), inflammation, and cerebrovascular function. Obesity-associated changes in gut microbiota composition may cause increased gut permeability and inflammation, therewith affecting cognitive function. Moreover, excess of WAT in obesity produces pro-inflammatory adipokines, leading to a low grade systemic peripheral inflammation, which is associated with decreased cognition. The blood-brain barrier also shows increased permeability, allowing among others, peripheral pro-inflammatory markers to access the brain, leading to neuroinflammation, especially in the hypothalamus, hippocampus and amygdala. Altogether, the interaction between the gut microbiota, WAT inflammation, and cerebrovascular integrity plays a significant role in the link between obesity and cognition. Future research should focus more on the interplay between gut microbiota, WAT, inflammation and cerebrovascular function to obtain a better understanding about the complex link between obesity and cognitive function in order to develop preventatives and personalized treatments.

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Gut microbiome is associated with thyroid nodule and functions

10.21203/rs.3.rs-16228/v1 ◽

2020 ◽

Author(s):

Suying Ding ◽

Ang Li ◽

Tiantian Li ◽

Xinxin Gao ◽

Hang Yan ◽

...

Keyword(s):

Gut Microbiota ◽

Thyroid Nodule ◽

Gut Microbiome ◽

Genome Wide Association Study ◽

Adult Population ◽

Low Grade ◽

Lower Grade ◽

High Grade ◽

Functional Richness ◽

Essential Components

Abstract Background: Thyroid nodule affects nearly half of the adult population. Accumulating evidence suggests that gut microbiota plays an important role in the thyroid disorders and functions, yet the association between gut microbiota capacity and thyroid nodule and function have not been studied comprehensively.Methods: We performed a gut microbiota whole-genome wide association study in 537 thyroid nodule participants and 725 controls from the general Chinese population. Thyroid nodules were with the Thyroid Imaging Reporting and Data System assessment.Results: Participants with the highest grade thyroid nodule had decreased gut microbial species and functional richness compared with controls and thyroid nodule with lower grade. Microbiota composition of the low-grade thyroid nodule was similar to that in controls rather than high-grade thyroid nodule. We found significant alternations of overall microbial functional composition in high-grade thyroid nodule but not the species composition, only a small portion of microbioal species were associated with high-grade thyroid nodule. The high-grade thyroid nodule gut microbiome was characterized by greater amino acid degradation and glycolysis, also with fewer Butyrivibrio and lower butyric acid production. Thyroid functions were positively associated with L-histidine and L-tyrosine related biosynthesis pathways, which are essential components of thyrotropin-releasing hormone and thyroxine, also corelated with broad nutrition metabolism pathways including fatty acids, B family vitamins and nucleotides. High-grade thyroid nodule discrimination models based on the gut microbiome and demography were validated using 294 independent samples and showed stable classification power.Conclusion: Our study comprehensively described the gut microbiome characteristics in thyroid nodule and suggested potiental role of the key gut microbiota-driven functional pathways in thyroid nodule and functions metabolism.

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SAT0623-HPR THE LIVED EXPERIENCES OF COGNITIVE DYSFUNCTION IN ADULTS WITH FIBROMYALGIA: A QUALITATIVE SYSTEMATIC REVIEW

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2119 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1271.1-1272

Author(s):

S. Derham ◽

J. Lewis ◽

E. Dures ◽

F. Cramp

Keyword(s):

Clinical Practice ◽

Cognitive Function ◽

Cognitive Dysfunction ◽

Lived Experiences ◽

Critical Appraisal ◽

Negative Impact ◽

Practice Research ◽

Future Research ◽

Poor Sleep ◽

Cognitive Changes

Background:Adults with fibromyalgia frequently report symptoms of cognitive dysfunction, often referred to as fibrofog. However primary research exploring cognitive dysfunction in the lives of adults with fibromyalgia is very limited (Kravitz and Katz, 2015).Objectives:The aim of this review was to (i) synthesise the qualitative literature on the lived experiences of cognitive dysfunction in adults with fibromyalgia, (ii) develop common themes through thematic analysis and (iii) identify knowledge gaps to inform future research and clinical practice in this area.Methods:Seven electronic databases (MEDLINE, Embase, CINAHL, PsycINFO, Amed, Scopus and OpenGrey), reference lists of key articles and two high impact qualitative journals were searched from 1990 to November 2018. Articles were eligible for inclusion if they reported primary qualitative data exploring the experiences of cognitive dysfunction in adults with fibromyalgia. Included studies were appraised using the Critical Appraisal Skills Programme (CASP) qualitative checklist and extracted data analysed using narrative synthesis. SD conducted critical appraisal and data extraction on all included studies. FC, JL and ED reviewed five papers each. All papers were reviewed by two co-authors. Of the 1413 records identified, 15 studies were selected for inclusion.Results:These studies included 208 women and 22 men with fibromyalgia, aged 18 to 72 years and representing seven different countries. Duration of diagnosis was four months to 34 years. Fourteen studies used interviews and one used focus groups. None of the included studies focussed exclusively on cognitive function in adults with fibromyalgia. Three studies identified themes specific to cognitive dysfunction and fibromyalgia symptoms. The remaining 12 studies presented relevant data intertwined with the overall lived experiences of fibromyalgia.Cognitive dysfunction, as a part of fibromyalgia, was often unpredictable. Problems with memory and concentration that were most commonly reported were emotionally distressing and affected functional and vocational activities. Participants found communication effortful, with a negative impact on work, leisure and social activities. Stress, fear and worry around perceived cognitive changes were commonly expressed. Lost employment or changed work roles and relationships, due to cognitive difficulties, had negative impacts for many participants. The terms cognitive dysfunction and fibrofog were used interchangeably within the studies, but lacked common definition. This introduced uncertainty around whether participants and authors were describing the same phenomenon.Conclusion:Adults with fibromyalgia experience unpredictable and emotionally impactful difficulties related to cognitive dysfunction. Functional impact was broad-reaching, particularly around work ability and lost employment opportunities. It is unclear how cognitive symptoms in fibromyalgia related to co-morbid symptoms such as pain, fatigue and poor sleep. Further research focusing on the full impact of cognitive function on the lives of adults with fibromyalgia is recommended to inform clinical practice. Research to establish clarity of definition of the terms cognitive dysfunction and fibrofog within fibromyalgia is highly recommended.References:[1]Kravitz H, Katz R. Fibrofog and fibromyalgia: a narrative review and implications for clinical practice. Rheumatology International. 2015;35(7):1115-25.Acknowledgments:This work is supported by the National Institute for Heath Research [ICA-PCAF-2018-01-078 to SD]Disclosure of Interests:Sandra Derham: None declared, Jenny Lewis: None declared, Emma Dures Grant/research support from: Independent Learning Grant from Pfizer, combined funding for a research fellow from Celgene, Abbvie and Novartis, Paid instructor for: A fee from Novartis to deliver training to nurses., Fiona Cramp: None declared

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The Gut Microbiota and Healthy Aging: A Mini-Review

Gerontology ◽

10.1159/000490615 ◽

2018 ◽

Vol 64 (6) ◽

pp. 513-520 ◽

Cited By ~ 59

Author(s):

Sangkyu Kim ◽

S. Michal Jazwinski

Keyword(s):

Gut Microbiota ◽

Individual Variation ◽

Gut Microbiome ◽

Chronological Age ◽

Low Grade ◽

Beneficial Effects ◽

Gut Dysbiosis ◽

Age Related ◽

Host Health ◽

Nutrient Signaling

The gut microbiota shows a wide inter-individual variation, but its within-individual variation is relatively stable over time. A functional core microbiome, provided by abundant bacterial taxa, seems to be common to various human hosts regardless of their gender, geographic location, and age. With advancing chronological age, the gut microbiota becomes more diverse and variable. However, when measures of biological age are used with adjustment for chronological age, overall richness decreases, while a certain group of bacteria associated with frailty increases. This highlights the importance of considering biological or functional measures of aging. Studies using model organisms indicate that age-related gut dysbiosis may contribute to unhealthy aging and reduced longevity. The gut microbiome depends on the host nutrient signaling pathways for its beneficial effects on host health and lifespan, and gut dysbiosis disrupting the interdependence may diminish the beneficial effects or even have reverse effects. Gut dysbiosis can trigger the innate immune response and chronic low-grade inflammation, leading to many age-related degenerative pathologies and unhealthy aging. The gut microbiota communicates with the host through various biomolecules, nutrient signaling-independent pathways, and epigenetic mechanisms. Disturbance of these communications by age-related gut dysbiosis can affect the host health and lifespan. This may explain the impact of the gut microbiome on health and aging.

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Gut Microbiome Alterations in Patients With Thyroid Nodules

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.643968 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ang Li ◽

Tiantian Li ◽

Xinxin Gao ◽

Hang Yan ◽

Jingfeng Chen ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Thyroid Nodules ◽

Genome Wide Association Study ◽

Adult Population ◽

Lower Grade ◽

High Grade ◽

Microbial Composition ◽

Thyroid Metabolism ◽

Relative Abundances

Thyroid nodules are found in nearly half of the adult population. Accumulating evidence suggests that the gut microbiota plays an important role in thyroid metabolism, yet the association between gut microbiota capacity, thyroid nodules, and thyroid function has not been studied comprehensively. We performed a gut microbiome genome-wide association study in 196 patients with thyroid nodules and 283 controls by using whole-genome shotgun sequencing. We found that participants with high-grade thyroid nodules have decreased number of gut microbial species and gene families compared with those with lower grade nodules and controls. There are also significant alterations in the overall microbial composition in participants with high-grade thyroid nodules. The gut microbiome in participants with high-grade thyroid nodules is characterized by greater amino acid degradation and lower butyrate production. The relative abundances of multiple butyrate producing microbes are reduced in patients with high-grade thyroid nodules and the relative abundances of L-histidine metabolism pathways are associated with thyrotropin-releasing hormone. Our study describes the gut microbiome characteristics in thyroid nodules and a gut-thyroid link and highlight specific gut microbiota as a potential therapeutic target to regulate thyroid metabolism.

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Relationship between the Japanese-style diet, gut microbiota, and dementia: a cross-sectional study

10.21203/rs.3.rs-255821/v1 ◽

2021 ◽

Author(s):

Naoki Saji ◽

Tsuyoshi Tsuduki ◽

Kenta Murotani ◽

Takayoshi Hisada ◽

Taiki Sugimoto ◽

...

Keyword(s):

Cognitive Function ◽

Gut Microbiota ◽

Cognitive Decline ◽

Gut Microbiome ◽

Cross Sectional Study ◽

Dietary Composition ◽

Microbial Metabolites ◽

Cross Sectional ◽

Fish And Shellfish ◽

Japanese Diet

Abstract Background Previous studies have shown associations between the gut microbiota, microbial metabolites, and cognitive decline. However, the effect of the dietary composition on such associations has not been fully investigated. Methods We performed a cross-sectional sub-analysis of data from our prospective hospital-based cohort study (the Gimlet study) to evaluate the relationships between dietary composition, cognitive decline, and the gut microbiota. All the participants of the Gimlet study had been provided with information regarding this sub-study in 2018. Patients were excluded if they were unable to provide sufficient data in the questionnaire regarding their dietary composition. We assessed their demographics, dietary composition, risk factors, cognitive function, results of brain imaging, gut microbiome, and microbial metabolites. On the basis of previous studies, a nine-component traditional Japanese diet index (JDI9), a 12-component modern JDI (JDI12), and a 12-component revised JDI (rJDI12), were defined. Higher JDI scores indicated greater conformity to the traditional Japanese diet. We then evaluated the relationships between the JDI scores, cognitive function, and the gut microbiome and microbial metabolites using multivariable logistic regression analyses. Results We analyzed data from 85 eligible patients (61% women; mean age: 74.6 ± 7.4 years; mean Mini-Mental State Examination score: 24 ± 5). Compared with participants with dementia, those without dementia were more likely to consume foods in the JDI12, including fish and shellfish (64.5% vs. 39.1%, P = 0.048), mushrooms (61.3% vs. 30.4%, P = 0.015), soybeans and soybean-derived foods (62.9% vs. 30.4%, P = 0.013), and coffee (71.0% vs. 43.5%, P = 0.024). There were non-significant trends towards lower fecal concentrations of gut microbial metabolites in participants with a more traditional Japanese diet. Participants with dementia had lower JDI9, JDI12, and rJDI12 scores than participants without dementia (dementia vs. non-dementia, median JDI9 score: 5 vs. 7, P = 0.049; JDI12: 7 vs. 8, P = 0.017; and rJDI12: 7 vs. 9, P = 0.006, respectively). Conclusions Adherence to a traditional Japanese diet was found to be inversely associated with cognitive decline and tended to be associated with lower concentrations of gut microbial metabolites. Trial registration: UMIN000031851.

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Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis

RMD Open ◽

10.1136/rmdopen-2019-001037 ◽

2019 ◽

Vol 5 (2) ◽

pp. e001037 ◽

Cited By ~ 11

Author(s):

Jean-Marie Berthelot ◽

Jérémie Sellam ◽

Yves Maugars ◽

Francis Berenbaum

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Cartilage Degradation ◽

Low Grade ◽

New Paradigm ◽

Healthy Human ◽

Human Cartilage ◽

Intact Cartilage ◽

Low Grade Inflammation

DNA of gut microbiota can be found in synovium of osteoarthritis and rheumatoid arthritis. This finding could result from the translocation of still alive bacteria from gut to joints through blood, since the diversified dormant microbiota of healthy human blood can be transiently resuscitated in vitro. The recent finding of gut microbiome in human cartilage, which differed between osteoarthritis and controls, suggests that a similar trafficking of dead or alive bacteria from gut microbiota physiologically occurs between gut and epiphysial bone marrow. Subchondral microbiota could enhance cartilage healing and transform components of deep cartilage matrix in metabolites with immunosuppressive properties. The differences of microbiome observed between hip and knee cartilage, either in osteoarthritis or controls, might be the counterpart of subtle differences in chondrocyte metabolism, themselves in line with differences in DNA methylation according to joints. Although bacteria theoretically cannot reach chondrocytes from the surface of intact cartilage, some bacteria enter the vascular channels of the epiphysial growth cartilage in young animals, whereas others can infect chondrocytes in vitro. In osteoarthritis, the early osteochondral plate angiogenesis may further enhance the ability of microbiota to locate close to the deeper layers of cartilage, and this might lead to focal dysbiosis, low-grade inflammation, cartilage degradation, epigenetic changes in chondrocytes and worsening of osteoarthritis. More studies on cartilage across different ethnic groups, weights, and according to age, are needed, to confirm the silent presence of gut microbiota close to human cartilage and better understand its physiologic and pathogenic significance.

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Dementia associated with alcohol and other drug use

International Psychogeriatrics ◽

10.1017/s1041610205001985 ◽

2005 ◽

Vol 17 (s1) ◽

pp. S109-S127 ◽

Cited By ~ 50

Author(s):

Gary K. Hulse ◽

Nicola T. Lautenschlager ◽

Robert J. Tait ◽

Osvaldo P. Almeida

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Drug Use ◽

Negative Impact ◽

Diagnostic Category ◽

Later Life ◽

Increased Risk ◽

Causal Pathway ◽

Chronic Use

The acute use of alcohol and several other licit and illicit drugs can affect mental state and cognitive function. The chronic use of certain drugs may also increase the risk of cognitive impairment and perhaps dementia in later life. This paper focuses on the long-term cognitive consequences of using alcohol, benzodiazepines, tobacco and cannabis. Currently available evidence indicates that mild to moderate alcohol consumption is not associated with increased risk of cognitive decline and may in fact have a protective effect against dementia, although heavy, long-term consumption is likely to have a negative impact on cognitive function. The degree that alcohol-related cognitive impairment must reach to be classified as dementia is currently obscure. Longer-term smoking is associated with increased risk of cognitive impairment and possibly dementia. The chronic use of benzodiazepines has been associated with increased risk of cognitive impairment but information relating to dementia remains inconclusive. The chronic use of cannabis may impair intellectual abilities but data on this topic remain sparse and difficult to interpret. In conclusion, there is evidence that some drugs contribute to the causal pathway that leads to the development of cognitive impairment but currently available data do not support the introduction of a separate diagnostic category of drug-induced dementia (such as alcohol-related dementia). Health promotion programs designed to decrease tobacco smoking and “harmful” alcohol use (and possibly other drug use) may decrease the burden of cognitive impairment and perhaps dementia in later life.

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Pet Ownership and Quality of Life: A Systematic Review of the Literature

Veterinary Sciences ◽

10.3390/vetsci8120332 ◽

2021 ◽

Vol 8 (12) ◽

pp. 332

Author(s):

Kristel J. Scoresby ◽

Elizabeth B. Strand ◽

Zenithson Ng ◽

Kathleen C. Brown ◽

Charles Robert Stilz ◽

...

Keyword(s):

Mental Health ◽

Negative Impact ◽

Positive Impact ◽

Adult Population ◽

The Body ◽

Future Research ◽

Pet Ownership ◽

Physical And Mental Health ◽

Prospective Longitudinal ◽

The Impact

Pet ownership is the most common form of human–animal interaction, and anecdotally, pet ownership can lead to improved physical and mental health for owners. However, scant research is available validating these claims. This study aimed to review the recent peer reviewed literature to better describe the body of knowledge surrounding the relationship between pet ownership and mental health. A literature search was conducted in May 2020 using two databases to identify articles that met inclusion/exclusion criteria. After title review, abstract review, and then full article review, 54 articles were included in the final analysis. Of the 54 studies, 18 were conducted in the general population, 15 were conducted in an older adult population, eight were conducted in children and adolescents, nine focused on people with chronic disease, and four examined a specific unique population. Forty-one of the studies were cross-sectional, 11 were prospective longitudinal cohorts, and two were other study designs. For each of the articles, the impact of pet ownership on the mental health of owners was divided into four categories: positive impact (n = 17), mixed impact (n = 19), no impact (n = 13), and negative impact (n = 5). Among the reviewed articles, there was much variation in population studied and study design, and these differences make direct comparison challenging. However, when focusing on the impact of pet ownership on mental health, the results were variable and not wholly supportive of the benefit of pets on mental health. Future research should use more consistent methods across broader populations and the development of a pet-ownership survey module for use in broad, population surveys would afford a better description of the true relationship of pet ownership and mental health.

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Comprehensive Bibliometric Analysis of the Kynurenine Pathway in Mood Disorders: Focus on Gut Microbiota Research

Frontiers in Pharmacology ◽

10.3389/fphar.2021.687757 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiuqing Zhu ◽

Jinqing Hu ◽

Shuhua Deng ◽

Yaqian Tan ◽

Chang Qiu ◽

...

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Citation Analysis ◽

Mood Disorders ◽

Bibliometric Analysis ◽

The United States ◽

Kynurenine Pathway ◽

Current Status ◽

Future Research ◽

Low Grade

Background: Emerging evidence implicates the dysregulated kynurenine pathway (KP), an immune-inflammatory pathway, in the pathophysiology of mood disorders (MD), including depression and bipolar disorder characterized by a low-grade chronic pro-inflammatory state. The metabolites of the KP, an important part of the microbiota-gut-brain axis, serve as immune system modulators linking the gut microbiota (GM) with the host central nervous system.Aim: This bibliometric analysis aimed to provide a first glimpse into the KP in MD, with a focus on GM research in this field, to guide future research and promote the development of this field.Methods: Publications relating to the KP in MD between the years 2000 and 2020 were retrieved from the Scopus and Web of Science Core Collection (WoSCC), and analyzed in CiteSpace (5.7 R5W), biblioshiny (using R-Studio), and VOSviewer (1.6.16).Results: In total, 1,064 and 948 documents were extracted from the Scopus and WoSCC databases, respectively. The publications have shown rapid growth since 2006, partly owing to the largest research hotspot appearing since then, “quinolinic acid.” All the top five most relevant journals were in the neuropsychiatry field, such as Brain Behavior and Immunity. The United States and Innsbruck Medical University were the most influential country and institute, respectively. Journal co-citation analysis showed a strong tendency toward co-citation of research in the psychiatry field. Reference co-citation analysis revealed that the top four most important research focuses were “kynurenine pathway,” “psychoneuroimmunology,” “indoleamine 2,3-dioxygenase,” and “proinflammatory cytokines,” and the most recent focus was “gut-brain axis,” thus indicating the role of the KP in bridging the GM and the host immune system, and together reflecting the field’s research foundations. Overlap analysis between the thematic map of keywords and the keyword burst analysis revealed that the topics “Alzheimer’s disease,” “prefrontal cortex,” and “acid,” were research frontiers.Conclusion: This comprehensive bibliometric study provides an updated perspective on research associated with the KP in MD, with a focus on the current status of GM research in this field. This perspective may benefit researchers in choosing suitable journals and collaborators, and aid in the further understanding of the field’s hotspots and frontiers, thus facilitating future research.

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Estradiol and high fat diet associate with changes in gut microbiota in female ob/ob mice

Scientific Reports ◽

10.1038/s41598-019-56723-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Kalpana D. Acharya ◽

Xing Gao ◽

Elizabeth P. Bless ◽

Jun Chen ◽

Marc J. Tetel

Keyword(s):

Weight Gain ◽

Gut Microbiota ◽

High Fat Diet ◽

Energy Homeostasis ◽

Low Grade ◽

High Fat ◽

Diet Induced Obesity ◽

Increased Risk ◽

17Β Estradiol ◽

Low Grade Inflammation

AbstractEstrogens protect against diet-induced obesity in women and female rodents. For example, a lack of estrogens in postmenopausal women is associated with an increased risk of weight gain, cardiovascular diseases, low-grade inflammation, and cancer. Estrogens act with leptin to regulate energy homeostasis in females. Leptin-deficient mice (ob/ob) exhibit morbid obesity and insulin resistance. The gut microbiome is also critical in regulating metabolism. The present study investigates whether estrogens and leptin modulate gut microbiota in ovariectomized ob/ob (obese) or heterozygote (lean) mice fed high-fat diet (HFD) that received either 17β-Estradiol (E2) or vehicle implants. E2 attenuated weight gain in both genotypes. Moreover, both obesity (ob/ob mice) and E2 were associated with reduced gut microbial diversity. ob/ob mice exhibited lower species richness than control mice, while E2-treated mice had reduced evenness compared with vehicle mice. Regarding taxa, E2 was associated with an increased abundance of the S24-7 family, while leptin was associated with increases in Coriobacteriaceae, Clostridium and Lactobacillus. Some taxa were affected by both E2 and leptin, suggesting these hormones alter gut microbiota of HFD-fed female mice. Understanding the role of E2 and leptin in regulating gut microbiota will provide important insights into hormone-dependent metabolic disorders in women.

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