Underlying Mechanisms behind the Brain–Gut–Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3694 - 3694

Published: March 26, 2024

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain–gut–liver axis and, consequently, increases cardiovascular risks and dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, syndrome are frequently present; these conditions related to lipogenesis systemic inflammation. This study aimed review connection between MAFLD. The inflammatory process, cellular alterations hepatocytes stellate cells, hypercaloric diet, sedentarism aggravate prognosis of patients with Thus, understand modulation physiopathology it is necessary include organokines involved this process (adipokines, myokines, osteokines, hepatokines) their clinical relevance project future perspectives condition bring light new possibilities therapeutic approaches. Adipokines responsible for activation distinct signaling different tissues, such as insulin pro-inflammatory cytokines, which important balancing substances avoid MAFLD its progression. Myokines improve quantity quality adipose contributing avoiding development Finally, hepatokines decisive improving or not progression through regulation anti-inflammatory organokines.

Language: Английский

---

RGS10 attenuates systemic immune dysregulation induced by chronic inflammatory stress

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 24, 2025

Abstract Regulator of G-protein signaling 10 (RGS10), a key homeostatic regulator immune cells, has been implicated in multiple diseases associated with aging and chronic inflammation including Parkinson’s Disease (PD). Interestingly, subjects idiopathic PD display reduced levels RGS10 subsets peripheral cells. Additionally, individuals have shown to increased activated cells cerebrospinal fluid (CSF) compared age-matched healthy controls. However, it is unknown whether the CSF also exhibit decreased RGS10. Utilizing Michael J. Fox Foundation Progression Markers Initiative (PPMI) study we found that are controls prodromal individuals. As circulating PD, hypothesized regulates cell responses systemic (CSI) prior onset neurodegeneration. To test this, induced CSI for 6 weeks C57BL6/J mice KO assess CNS-associated responses. We deficiency synergizes induce bias inflammatory cytotoxic populations, reduction antigen presentation machinery blood as well around brain most notable males. These results highlight an important response implicate potential contributor development dysregulation PD.

Language: Английский

---

Inflammatory bowel disease and neuropsychiatric disorders: Mechanisms and emerging therapeutics targeting the microbiota-gut-brain axis

Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 108831 - 108831

Published: Feb. 1, 2025

Language: Английский

---

Comparative analysis of Parkinson’s and inflammatory bowel disease gut microbiomes reveals shared butyrate-producing bacteria depletion

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 19, 2025

Abstract Epidemiological studies reveal that inflammatory bowel disease (IBD) is associated with an increased risk of Parkinson’s (PD). Gut dysbiosis has been documented in both PD and IBD, however it currently unknown whether gut underlies the epidemiological association between diseases. To identify shared distinct features IBD microbiome, we recruited 54 PD, 26 16 healthy control individuals performed first joint analysis metagenomes. Larger, publicly available metagenomic datasets were also analyzed to validate extend our findings. Depletions short-chain fatty acid (SCFA)-producing bacteria, including Roseburia intestinalis, Faecalibacterium prausnitzii, Anaerostipes hadrus , Eubacterium rectale as well depletion SCFA-synthesis pathways detected across datasets, suggesting these microbes may influence for development.

Language: Английский

---

Experimentally induced colitis impacts myelin development and home-cage behavior in young pigs regardless of supplementation with oral gamma-cyclodextrin-encapsulated tributyrin

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: March 31, 2025

Colitis, a chronic intestinal disorder that causes inflammation of the colonic mucosa, has been linked with structural brain abnormalities. To combat inflammation, researchers have investigated how nutritional supplementation, such as butyric acid, may ameliorate untoward effects. By encapsulating and using conjugates butyrate, butyrate glycerides (i.e., tributyrin), slower release to lower portions gastrointestinal tract can be achieved. Additionally, supplementation supporting function regulating integrity. In present study, total 24 intact male pigs were artificially reared randomly assigned 1 3 treatment conditions: (1) control milk replacer (CON), (2) plus oral dextran sodium sulfate (DSS) induce colitis, or (3) supplemented 9.0 mM gamma-cyclodextrin encapsulated tributyrin (TBCD) DSS (TBCD+DSS). Pigs orally administered treatments daily from postnatal day (PND) 14-18. Continuous video recording began on PND ceased 27 28, videos processed analyzed for home-cage tracking behavior. On 26 27, underwent neuroimaging procedures assess overall anatomy (MPRAGE), microstructure (DTI), myelin (MWF). Home-cage spatial preference was not altered prior dosing during study period. However, TBCD+DSS spent less (p < 0.05) time within quadrant 4 when compared CON pigs. Across almost all 29 regions assessed, absolute volumes observed smaller in group groups. once individual assessed relative whole brain, most effects dissipated other than gray matter volume = 0.041). Diffusivity found several across groups, thereby indicating differences fiber organization. areas like hippocampus thalamus, fractional anisotropy (FA) values highest given treatment, diffusion metrics (mean, radial, axial diffusivity) lowest same more organized cellular structure. Several trends various regions. Lastly, water fraction (MWF) DSS-treated groups left/right cortices. Overall, organization myelination by experimentally induced colitis contrary expectations, did these Future work is warranted investigate protective mechanisms colitis.

Language: Английский

---

The modulatory influence of humic acid on cognitive impairment and neurobehavioral changes induced by colitis in adult male Wistar rats

Nutrire, Journal Year: 2024, Volume and Issue: 49(2)

Published: Sept. 12, 2024

Language: Английский

---

RGS10 Attenuates Systemic Immune Dysregulation Induced by Chronic Inflammatory Stress

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract Regulator of G-protein signaling 10 (RGS10), a key homeostatic regulator immune cells, has been implicated in multiple diseases associated with aging and chronic inflammation including Parkinson’s Disease (PD). Interestingly, subjects idiopathic PD display reduced levels RGS10 subsets peripheral cells. Additionally, individuals have shown to increased activated cells cerebral spinal fluid (CSF) compared age-matched healthy controls. However, it is unknown whether CSF-resident also exhibit decreased RGS10. Therefore, we performed an analysis the proteomic database CSF from Michael J. Fox Foundation Progression Markers Initiative (PPMI) study. We found that are controls prodromal individuals. Moreover, find decrease age but not progression males less than females PD. Importantly, studies established association between systemic (CSI) neurodegenerative diseases, such as PD, known sources CSI identified risk factors for developing PD; however, role cell dysregulation this process underexplored. As circulating hypothesized regulates responses prior onset neurodegeneration. To test this, induced 6 weeks C57BL6/J mice KO assess CNS-associated responses. deficiency synergizes induce bias inflammatory cytotoxic populations, reduction antigen presentation blood well around brain most notable males. These results highlight important response implicate potential contributor development

Language: Английский

---

Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 12, 2024

Parkinson's disease (PD) is characterized by a decades-long prodrome, consisting of collection non-motor symptoms that emerges prior to the motor manifestation disease. Of these symptoms, gastrointestinal dysfunction and deficits attributed central norepinephrine (NE) loss, including mood changes sleep disturbances, are frequent in PD population emerge early Evidence mounting injury inflammation gut locus coeruleus (LC), respectively, underlie systems progression PD. In this study, we generate novel two-hit mouse model captures both features, using dextran sulfate sodium (DSS) induce N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesion LC. We first confirmed specificity DSP-4 for NE neurochemical methods fluorescence light-sheet microscopy cleared tissue, established DSS-induced outcomes periphery, weight gross indices systemic inflammation, loss tight junction proteins colonic epithelium, markers were unaffected with pre-administration. then measured alterations neuroimmune gene expression ventral midbrain response DSS treatment alone as well extent which LC modified response. observed colitis activates key cytokines chemokines only presence typical DSS-associated blunted pre-LC lesioning DSP-4. all, study supports growing appreciation neuroprotective against inflammation-induced brain draws attention potential NEergic interventions exert disease-modifying effects under conditions where peripheral may compromise dopaminergic neurons increase risk development

Language: Английский

---

The Modulatory Influence of Humic Acid on Cognitive Impairment and Neurobehavioral Changes Induced by Colitis in Adult Male Wistar Rats

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 31, 2024

Objectives: Ulcerative colitis (UC) is regarded as a chronic inflammatory disorder that involves any part of the colon. It typically presents with symptoms such abdominal pain, bloody diarrhea, rectal urgency, and comorbid neuropsychiatric manifestations anxiety, depression, cognitive impairment. Different drugs are used in management ulcerative colitis, including medicinal plants other substances from organic sources. This study was conducted to investigate role humic acid attenuating neurobehavioral disorders caused by Dextran sulfate sodium-induced male Wistar rats. Methods: Twenty rats were randomly assigned into groups (n = 5). Group 1[control group]; group 2 [5% sodium (DSS) without additional treatment]; 3 DSS followed administration (30 mg/kg)]; 4 sulfasalazine (200 mg/kg)]. Behavioral patterns assessed pre-colitis induction, immediately after induction on day 5, drug treatment (post-treatment). The disease activity index for obtained days 1, 3, 10 experimental duration. Thereafter, colons harvested macroscopic assessment colitis. Data analyzed using ANOVA at p < 0.05. Results:Findings revealed significantly attenuated depression-like behavior, impairment triggered via modulations brain enzymatic antioxidants neurochemicals. Conclusion:This shows suppresses colitis-induced changes have neuroprotective effects addition its gastroprotective properties.

Language: Английский

---

Unveiling the Journey from the Gut to the Brain: Decoding Neurodegeneration–Gut Connection in Parkinson’s Disease

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(13), P. 2454 - 2469

Published: June 19, 2024

Parkinson's disease, a classical motor disorder affecting the dopaminergic system of brain, has been as disease but this notion now viewed differently pathology begins in gut and then gradually moves up to brain regions. The microorganisms play critical role maintaining physiology from barrier integrity secretion microbial products that maintain healthy state. subsequently alters normal composition microbes causes deleterious effects ultimately trigger strong neuroinflammation nonmotor symptoms along with characteristic synucleopathy, pathological hallmark disease. Understanding complex pathomechanisms distinct established preclinical models is primary goal researchers decipher how exactly central effect; quest led many answered some open-ended questions for researchers. We summarize popular opinions contrasting views, concise footsteps treatment strategies targeting gastrointestinal system.

Language: Английский

---