Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice

2019 ◽  
Vol 11 (518) ◽  
pp. eaau4760 ◽  
Author(s):  
Parag Kundu ◽  
Hae Ung Lee ◽  
Isabel Garcia-Perez ◽  
Emmy Xue Yun Tay ◽  
Hyejin Kim ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Skeletal Muscle Mass ◽  
Energy Homeostasis ◽  
Fibroblast Growth Factor 21 ◽  
Germ Free ◽  
Beneficial Effects ◽  
Similar Weight ◽  
Old Donor ◽  
Old Mice ◽  
The Brain

The gut microbiota evolves as the host ages, yet the effects of these microbial changes on host physiology and energy homeostasis are poorly understood. To investigate these potential effects, we transplanted the gut microbiota of old or young mice into young germ-free recipient mice. Both groups showed similar weight gain and skeletal muscle mass, but germ-free mice receiving a gut microbiota transplant from old donor mice unexpectedly showed increased neurogenesis in the hippocampus of the brain and increased intestinal growth. Metagenomic analysis revealed age-sensitive enrichment in butyrate-producing microbes in young germ-free mice transplanted with the gut microbiota of old donor mice. The higher concentration of gut microbiota–derived butyrate in these young transplanted mice was associated with an increase in the pleiotropic and prolongevity hormone fibroblast growth factor 21 (FGF21). An increase in FGF21 correlated with increased AMPK and SIRT-1 activation and reduced mTOR signaling. Young germ-free mice treated with exogenous sodium butyrate recapitulated the prolongevity phenotype observed in young germ-free mice receiving a gut microbiota transplant from old donor mice. These results suggest that gut microbiota transplants from aged hosts conferred beneficial effects in responsive young recipients.

scholarly journals Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1018
Author(s):  
Caitlyn A. Mullins ◽  
Ritchel B. Gannaban ◽  
Md Shahjalal Khan ◽  
Harsh Shah ◽  
Md Abu B. Siddik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Homeostasis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Obesity Prevalence ◽  
Beneficial Effects ◽  
The Brain

Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed.

scholarly journals The gut microbiota influences skeletal muscle mass and function in mice

2019 ◽  
Vol 11 (502) ◽  
pp. eaan5662 ◽  
Author(s):  
Shawon Lahiri ◽  
Hyejin Kim ◽  
Isabel Garcia-Perez ◽  
Musarrat Maisha Reza ◽  
Katherine A. Martin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Gut Microbiota ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Neuromuscular Junctions ◽  
Short Chain Fatty Acids ◽  
Germ Free ◽  
Mouse Skeletal Muscle ◽  
And Function

The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked a gut microbiota to the skeletal muscle of pathogen-free mice that had a gut microbiota. Compared to pathogen-free mouse skeletal muscle, germ-free mouse skeletal muscle showed atrophy, decreased expression of insulin-like growth factor 1, and reduced transcription of genes associated with skeletal muscle growth and mitochondrial function. Nuclear magnetic resonance spectrometry analysis of skeletal muscle, liver, and serum from germ-free mice revealed multiple changes in the amounts of amino acids, including glycine and alanine, compared to pathogen-free mice. Germ-free mice also showed reduced serum choline, the precursor of acetylcholine, the key neurotransmitter that signals between muscle and nerve at neuromuscular junctions. Reduced expression of genes encoding Rapsyn and Lrp4, two proteins important for neuromuscular junction assembly and function, was also observed in skeletal muscle from germ-free mice compared to pathogen-free mice. Transplanting the gut microbiota from pathogen-free mice into germ-free mice resulted in an increase in skeletal muscle mass, a reduction in muscle atrophy markers, improved oxidative metabolic capacity of the muscle, and elevated expression of the neuromuscular junction assembly genes Rapsyn and Lrp4. Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.

scholarly journals Interplay of Good Bacteria and Central Nervous System: Cognitive Aspects and Mechanistic Considerations

2021 ◽  
Vol 15 ◽  
Author(s):  
Mahmoud Salami
Keyword(s):  
Gut Microbiota ◽  
Cognitive Processing ◽  
Clinical Problem ◽  
The Body ◽  
Brain Diseases ◽  
Normal Brain ◽  
Beneficial Effects ◽  
Normal Brain Function ◽  
The Brain ◽  
Common Clinical Problem

The human gastrointestinal tract hosts trillions of microorganisms that is called “gut microbiota.” The gut microbiota is involved in a wide variety of physiological features and functions of the body. Thus, it is not surprising that any damage to the gut microbiota is associated with disorders in different body systems. Probiotics, defined as living microorganisms with health benefits for the host, can support or restore the composition of the gut microbiota. Numerous investigations have proved a relationship between the gut microbiota with normal brain function as well as many brain diseases, in which cognitive dysfunction is a common clinical problem. On the other hand, increasing evidence suggests that the existence of a healthy gut microbiota is crucial for normal cognitive processing. In this regard, interplay of the gut microbiota and cognition has been under focus of recent researches. In the present paper, I review findings of the studies considering beneficial effects of either gut microbiota or probiotic bacteria on the brain cognitive function in the healthy and disease statuses.

scholarly journals Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals

2021 ◽  
Vol 22 (22) ◽  
pp. 12551
Author(s):  
Silvia Diviccaro ◽  
Valentina Caputi ◽  
Lucia Cioffi ◽  
Silvia Giatti ◽  
Joshua M. Lyte ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Steroid Hormones ◽  
Endocrine System ◽  
Neuroactive Steroids ◽  
Brain Functioning ◽  
Germ Free ◽  
Liquid Chromatography Tandem Mass ◽  
Nervous Function ◽  
The Impact ◽  
The Brain

Steroid hormones are essential biomolecules for human physiology as they modulate the endocrine system, nervous function and behaviour. Recent studies have shown that the gut microbiota is directly involved in the production and metabolism of steroid hormones in the periphery. However, the influence of the gut microbiota on levels of steroids acting and present in the brain (i.e., neuroactive steroids) is not fully understood. Therefore, using liquid chromatography–tandem mass spectrometry, we assessed the levels of several neuroactive steroids in various brain areas and the plasma of germ-free (GF) male mice and conventionally colonized controls. The data obtained indicate an increase in allopregnanolone levels associated with a decrease in those of 5α-androstane-3α, 17β-diol (3α-diol) in the plasma of GF mice. Moreover, an increase of dihydroprogesterone and isoallopregnanolone in the hippocampus, cerebellum, and cerebral cortex was also reported. Changes in dihydrotestosterone and 3α-diol levels were also observed in the hippocampus of GF mice. In addition, an increase in dehydroepiandrosterone was associated with a decrease in testosterone levels in the hypothalamus of GF mice. Our findings suggest that the absence of microbes affects the neuroactive steroids in the periphery and the brain, supporting the evidence of a microbiota-mediated modulation of neuroendocrine pathways involved in preserving host brain functioning.

scholarly journals Genetic Evidence Supporting Fibroblast Growth Factor 21 Signalling as a Pharmacological Target for Cardiometabolic Outcomes and Alzheimer’s Disease

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1504
Author(s):  
Susanna C. Larsson ◽  
Dipender Gill
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Energy Homeostasis ◽  
Disease Risk ◽  
Fibroblast Growth Factor 21 ◽  
Clinical Effects ◽  
Fibroblast Growth ◽  
Beneficial Effects

Fibroblast growth factor 21 (FGF21) is a human metabolic hormone whose effects include modification of macronutrient preference and energy homeostasis. In animal models, FGF21 has been shown to have beneficial effects on cardiometabolic outcomes, Alzheimer’s disease risk and lifespan. In this study, the single-nucleotide polymorphism rs838133 in the FGF21 gene region was leveraged to investigate the potential clinical effects of targeting FGF21. The FGF21 G allele was associated with lower intakes of total sugars and alcohol, and higher intakes of protein and fat as well as favourable with lipid levels, blood pressure traits, waist-to-hip ratio, systemic inflammation, cardiovascular outcomes, Alzheimer’s disease risk and lifespan. These findings may be used to anticipate the effects of pharmacologically increasing FGF21 signalling.

scholarly journals Modulation of the gut microbiota-adipose tissue-muscle interactions by prebiotics

2021 ◽  
Author(s):  
Julie Rodriguez ◽  
Nathalie M Delzenne
Keyword(s):  
Adipose Tissue ◽  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Metabolic Functions ◽  
Promising Strategy ◽  
Gut Hormone ◽  
Intestinal Functions ◽  
Host Metabolism ◽  
The Impact ◽  
The Brain

The gut microbiota is now widely recognized as an important factor contributing to the regulation of host metabolic functions. Numerous studies describe an imbalance in the gut microbial ecosystem in response to an energy-dense diet that drives the development of metabolic disorders. In this context, the manipulation of the gut microbiota by food components acting as prebiotics appears as a promising strategy. Several studies have already investigated the beneficial potency of prebiotics, mostly inulin type fructans, on host metabolism and key intestinal functions including gut hormone release. For the last 20 years, several non-digestible compounds present in food have been shown to modulate the gut microbiota and influence host metabolism in essential organs involved in the control of energy homeostasis. To date, numerous reviews summarize the impact of prebiotics on the liver or the brain. Here we propose to describe the mechanisms by which prebiotics, through modulation of the gut microbiota and endocrine functions, modulates the metabolic cross-talk communication between the gut, the adipose tissue and skeletal muscles.

The effects of probiotics and prebiotics on gastrointestinal and behavioural symptoms in autism spectrum disorder

2021 ◽  
Vol 16 ◽  
Author(s):  
José Guevara-Gonzaléz ◽  
José Guevara-Campos ◽  
Lucía González ◽  
Omar Cauli
Keyword(s):  
Gut Microbiota ◽  
Autism Spectrum ◽  
Current Evidence ◽  
Unknown Etiology ◽  
Behavioural Symptoms ◽  
Beneficial Effects ◽  
Behavioral Abnormalities ◽  
Spectrum Disorders ◽  
Different Strains ◽  
The Brain

Background: Autism spectrum disorders (ASDs) are a group of prevalent neuropsychiatric disorders. They present a complex and unknown etiology, which in most cases includes significant peripheral alterations outside the brain such as in the composition of gut microbiota. Because the gut microbiota is involved in modulating the gut–brain axis, several studies have suggested that the microbiome in the gut can modify metabolites which are able to cross the blood–brain barrier and modulate brain function. Methods: we reviewed the current evidence regarding microbiota alterations in patients with ASD and the effects of the administration of probiotics and prebiotics in these patients, both in terms of gastrointestinal and behavioural symptoms. Results: Administration of a probiotic formulation containing different strains of Lactobacillus (L. acidophilus, L. rhamnosus, and others) and Bifidobacteria had beneficial effects upon these aforementioned symptoms and their use is recommended in a subgroup of ASD patients that present gastrointestinal disturbances, Nonetheless, the types of gastrointestinal disturbances that most benefit from such interventions remains to be elucidated in order to personalize the medical approaches. Conclusion: Recent clinical studies have shown that probiotic treatments can regulate the gut microbiota and may result in improvements in some behavioral abnormalities associated with ASD. Trials using prebiotic fibers or synbiotics preparations are still lacking and necessary in order to deep in such therapeutic strategies in ASD with comorbid gastrointestinal disrturbances

scholarly journals Brain Neurotransmitter Modulation by Gut Microbiota in Anxiety and Depression

2021 ◽  
Vol 9 ◽  
Author(s):  
Fei Huang ◽  
Xiaojun Wu
Keyword(s):  
Mental Health ◽  
Gut Microbiota ◽  
Human Brain ◽  
Intestinal Microbiota ◽  
Mental Illnesses ◽  
Anxiety And Depression ◽  
Rodent Models ◽  
Germ Free ◽  
Brain Neurotransmitter ◽  
The Brain

Anxiety and depression are highly prevalent mental illnesses worldwide and have long been thought to be closely associated to neurotransmitter modulation. There is growing evidence indicating that changes in the composition of the gut microbiota are related to mental health including anxiety and depression. In this review, we focus on combining the intestinal microbiota with serotonergic, dopaminergic, and noradrenergic neurotransmission in brain, with special emphasis on the anxiety- and depression-like behaviors in stress-related rodent models. Therefore, we reviewed studies conducted on germ-free rodents, or in animals subjected to microbiota absence using antibiotics, as well as via the usage of probiotics. All the results strongly support that the brain neurotransmitter modulation by gut microbiota is indispensable to the physiopathology of anxiety and depression. However, a lot of work is needed to determine how gut microbiota mediated neurotransmission in human brain has any physiological significance and, if any, how it can be used in therapy. Overall, the gut microbiota provides a novel way to alter neurotransmitter modulation in the brain and treat gut–brain axis diseases, such as anxiety and depression.

scholarly journals Therapeutic Potential of Various Plant-Based Fibers to Improve Energy Homeostasis via the Gut Microbiota

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3470
Author(s):  
Taylor M. Martinez ◽  
Rachel K. Meyer ◽  
Frank A. Duca
Keyword(s):  
Gut Microbiota ◽  
Dietary Fiber ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Corn Fiber ◽  
Health Issues ◽  
Obesity Epidemic ◽  
Beneficial Effects ◽  
Markers Of Inflammation ◽  
High Amylose

Obesity is due in part to increased consumption of a Western diet that is low in dietary fiber. Conversely, an increase in fiber supplementation to a diet can have various beneficial effects on metabolic homeostasis including weight loss and reduced adiposity. Fibers are extremely diverse in source and composition, such as high-amylose maize, β-glucan, wheat fiber, pectin, inulin-type fructans, and soluble corn fiber. Despite the heterogeneity of dietary fiber, most have been shown to play a role in alleviating obesity-related health issues, mainly by targeting and utilizing the properties of the gut microbiome. Reductions in body weight, adiposity, food intake, and markers of inflammation have all been reported with the consumption of various fibers, making them a promising treatment option for the obesity epidemic. This review will highlight the current findings on different plant-based fibers as a therapeutic dietary supplement to improve energy homeostasis via mechanisms of gut microbiota.

scholarly journals The Microbiota and the Gut–Brain Axis in Controlling Food Intake and Energy Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 5830
Author(s):  
Marina Romaní-Pérez ◽  
Clara Bullich-Vilarrubias ◽  
Inmaculada López-Almela ◽  
Rebeca Liébana-García ◽  
Marta Olivares ◽  
...  
Keyword(s):  
Food Intake ◽  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Scientific Evidence ◽  
Short Chain Fatty Acids ◽  
Nutrient Sensing ◽  
Feeding Time ◽  
Dietary Composition ◽  
Biological Products ◽  
The Brain

Obesity currently represents a major societal and health challenge worldwide. Its prevalence has reached epidemic proportions and trends continue to rise, reflecting the need for more effective preventive measures. Hypothalamic circuits that control energy homeostasis in response to food intake are interesting targets for body-weight management, for example, through interventions that reinforce the gut-to-brain nutrient signalling, whose malfunction contributes to obesity. Gut microbiota–diet interactions might interfere in nutrient sensing and signalling from the gut to the brain, where the information is processed to control energy homeostasis. This gut microbiota–brain crosstalk is mediated by metabolites, mainly short chain fatty acids, secondary bile acids or amino acids-derived metabolites and subcellular bacterial components. These activate gut–endocrine and/or neural-mediated pathways or pass to systemic circulation and then reach the brain. Feeding time and dietary composition are the main drivers of the gut microbiota structure and function. Therefore, aberrant feeding patterns or unhealthy diets might alter gut microbiota–diet interactions and modify nutrient availability and/or microbial ligands transmitting information from the gut to the brain in response to food intake, thus impairing energy homeostasis. Herein, we update the scientific evidence supporting that gut microbiota is a source of novel dietary and non-dietary biological products that may beneficially regulate gut-to-brain communication and, thus, improve metabolic health. Additionally, we evaluate how the feeding time and dietary composition modulate the gut microbiota and, thereby, the intraluminal availability of these biological products with potential effects on energy homeostasis. The review also identifies knowledge gaps and the advances required to clinically apply microbiome-based strategies to improve the gut–brain axis function and, thus, combat obesity.

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