Opioid-induced dysbiosis of maternal gut microbiota during gestation alters offspring gut microbiota and pain sensitivity

Gut Microbes, Journal Year: 2023, Volume and Issue: 16(1)

Published: Dec. 18, 2023

There has been a rapid increase in neonates born with history of prenatal opioid exposure. How exposure affects pain sensitivity offspring is interest, as this may perpetuate the epidemic. While few studies have reported hypersensitivity to thermal pain, potential mechanisms not described. This study posits that alterations gut microbiome underly prenatally methadone-exposed 3-week-old male offspring, which were generated using mouse model methadone Fecal samples collected from dams and their subjected 16s rRNA sequencing. Thermal mechanical assessed tail flick Von Frey assays. Transcriptomic changes whole brain or saline-exposed investigated RNA-sequencing, midbrain sections these animals qPCR profiling genes related neuropathic inflammatory pathways. Prenatal increased elevated serum levels IL-17a. Taxonomical analysis revealed resulted significant fecal microbiota composition, including depletion Lactobacillus, Bifidobacterium, Lachnospiracea sp relative abundance Akkermansia, Clostridium sensu stricto 1, Lachnoclostridium. Supplementation probiotic VSL#3 rescued offspring. Similarly, cross-fostering control also attenuated opioid-exposed Modulation maternal neonatal probiotics transcriptional immune-related signaling Together, our work provides compelling evidence gut-brain-axis mediating

Language: Английский

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Microbiome and physical activity

Advances in genetics, Journal Year: 2024, Volume and Issue: unknown, P. 409 - 450

Published: Jan. 1, 2024

Language: Английский

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Dysbiosis is associated with the behavioral phenotype observed in the triple-hit Wisket rat model of schizophrenia

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 111276 - 111276

Published: Jan. 1, 2025

Language: Английский

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Dietary Fatty Acid Composition Alters Gut Microbiome in Mice with Obesity-Induced Peripheral Neuropathy

Nutrients, Journal Year: 2025, Volume and Issue: 17(4), P. 737 - 737

Published: Feb. 19, 2025

Background: Peripheral neuropathy (PN), a complication of diabetes and obesity, progresses through complex pathophysiology. Lifestyle interventions to manage systemic metabolism are recommended prevent or slow PN, given the multifactorial risks obesity. A high-fat diet rich in saturated fatty acids (SFAs) induces which monounsaturated (MUFAs) rescues, independent weight loss, suggesting factors beyond impact nerve health. Interest has grown gut microbiome mechanisms is characterized by distinct microbiota signature that correlates with sciatic lipidome. Methods: Herein, we postulated SFA- versus MUFA-rich would composition correlate PN development. To assess causality, performed fecal transplantation (FMT) from donor mice fed lean recipient assessed metabolic phenotypes. Results: We found SFA-rich altered community structure, partially reversed. metrics correlated several microbial families, some containing genera feasible action for microbiome-mediated effects on PN. SFA MUFA FMT did not phenotypes although marginally induced motor Conclusions: The involvement diet-mediated changes gut–nerve axis may warrant further study.

Language: Английский

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Intestinal dysbiosis during pregnancy and microbiota-associated impairments in offspring

Frontiers in Microbiomes, Journal Year: 2025, Volume and Issue: 4

Published: March 20, 2025

The maternal microbiome is increasingly being recognized as a key determinant in various neonatal health outcomes, including offspring immunity, metabolism, brain function, and behavior. While the oral, vaginal, skin, gut microbiota are significant contributors to offspring’s postnatal microbial seeding, composition diversity of during pregnancy seems be critical shaping even prior birth. Growing evidence suggests that balance among groups their interactions with host crucial for health. Dysbiotic communities early life may lead disease processes offspring, though specific by which microbes affect development unknown. Here, we summarize research examining shifts pregnancy, effects on infant outcomes. We also discuss current theories how gastrointestinal (GI) tract influences probiotics perinatal period

Language: Английский

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Pathological evaluation of the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy

Pathology International, Journal Year: 2024, Volume and Issue: 74(8), P. 438 - 453

Published: June 18, 2024

Currently, there are more than 10 million patients with diabetes mellitus in Japan. Therefore, the need to explore pathogenesis of and complications leading its cure is becoming increasingly urgent. Pathological examination pancreatic tissues from type 2 reveals a decrease volume beta cells because combination various stresses. In human diabetes, islet amyloid deposition unique pathological change characterized by proinflammatory macrophage (M1) infiltration into islets. The changes pancreas were different according clinical factors, which suggests that can be further subclassified based on pathology. On other hand, diabetic peripheral neuropathy most frequent complication. early neuropathy, M1 sciatic nerve evokes oxidative stress or attenuates retrograde axonal transport, as clearly demonstrated vitro live imaging. Furthermore, parasympathetic density cell inversely correlated Goto-Kakizaki rats, suggesting itself may contribute volume. These findings suggest interrelated.

Language: Английский

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Tryptophan metabolism and small fibre neuropathy: a correlation study

Brain Communications, Journal Year: 2024, Volume and Issue: 6(2)

Published: Jan. 1, 2024

Small nerve fibres located in the epidermis sense pain. Dysfunction of these decreases pain threshold known as small fibre neuropathy. Diabetes mellitus is accompanied by metabolic changes other than glucose, synergistically eliciting These findings suggest that various may be involved Herein, we explored correlation between sensation and plasma metabolites healthy Japanese subjects. The evaluated from intraepidermal electrical stimulation was used to quantify a total 1021 individuals 2017 Iwaki Health Promotion Project. Participants with index <0.20 mA were categorized into index-low group (

Language: Английский

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Modulating the Gut Microbiota and Metabolites with Traditional Chinese Medicines: An Emerging Therapy for Type 2 Diabetes Mellitus and Its Complications

Molecules, Journal Year: 2024, Volume and Issue: 29(12), P. 2747 - 2747

Published: June 9, 2024

Currently, an estimated 537 million individuals are affected by type 2 diabetes mellitus (T2DM), the occurrence of which is invariably associated with complications. Glucose-lowering therapy remains main treatment for alleviating T2DM. However, conventional antidiabetic agents fraught numerous adverse effects, notably elevations in blood pressure and lipid levels. Recently, use traditional Chinese medicines (TCMs) their constituents has emerged as a preferred management strategy aimed at curtailing progression its complications fewer effects. Increasing evidence indicates that gut microbiome disturbances involved development T2DM This regulation depends on various metabolites produced microbes interactions host organs. TCMs’ interventions have demonstrated ability to modulate intestinal bacterial microbiota, thereby restoring homeostasis ameliorating metabolic disorders. review delves into alterations microbiota patients how TCMs regulates facilitating Additionally, we also discuss prospective avenues research natural products advance therapy.

Language: Английский

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Moderate cryptoxanthin intake correlates with maintenance of a proper PINT index in a general Japanese population

Nutritional Neuroscience, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 11

Published: July 25, 2024

Small fibre neuropathy (SFN) is an early manifestation of diabetic polyneuropathy. Although oxidative stress, inflammation and change intestinal bacterial population are assumed to be their pathogenesis, the effects dietary nutrition have not been evaluated. The relationship between intake pain sensation was evaluated in Japanese population.

Language: Английский

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Serine supplementation: Is it a new option for the treatment of diabetic polyneuropathy?

Journal of Diabetes Investigation, Journal Year: 2023, Volume and Issue: 14(10), P. 1157 - 1159

Published: June 25, 2023

Subjects with diabetes develop marked disturbances in amino acid metabolism and the concentration plasma tissues. Most consistently, levels of branched-chain acids (BCAAs) aromatic are increased, l-serine glycine decreased1. Aberrant nonessential is involved pathogenesis diabetes. Elevated BCAAs have been associated insulin resistance type 2 since 1960s2. A cluster obesity-associated changes specific acid, acylcarnitine, organic metabolites obese compared lean subjects was also resistance. Although it speculated that aminoacidemia play a role development diabetic complications, their has not sufficiently elucidated detail. Diabetic peripheral neuropathy (DPN) most frequent complication among patients. Its symptoms pain, hyperalgesia, hypoalgesia, paralysis, which can decrease quality life In neuropathy, nerve fibers affected from prediabetic stage. Because retrograde-type small located epidermis or cornea first degraded. Small consist myelinated Aδ unmyelinated C fibers. fiber disorder these fibers, manifesting as spontaneous pain loss sensation reduction density. As progresses, large decreased segmental demyelination microvascular changes, such thickening vascular wall stenosis intraneuronal vessels. Without proper treatment, patients paralysis ulcer formation on foot. To date, thought to be caused by aberrant glucose neuronal cells, Schwann cells endothelial nervous system. Abnormal glycemic elicits dysfunction activation polyol pathway, protein kinase C, advanced glycation end products its receptor, receptor for product (RAGE) oxidative stress, inflammation. Clinically, addition hyperglycemia, metabolic syndrome, including dyslipidemia, obesity hypertension, well known contributor neuropathy. fatty metabolism, recent metabolomics studies revealed involvement another metabolite, glucosamine, Lower baseline asparagine glutamine were correlated cardiovascular autonomic sample 1 diabetes3. Thus, today, recognized only abnormal but complex condition failure other nutrients involved. However, full picture yet elucidated. this context, Handzlik et al.4 recently reported Nature combination serine deficiency dyslipidemia cause experimental mainly consisting supplementation delay onset (Figure 1). The db/db mouse model, conventional showed reductions hepatic renal approximately 30% relative wild-type mice, pools reduced 30–50% liver, kidney, inguinal white adipose tissue, plasma. expression level components encoding cleavage system increased whereas genes de novo synthesis significantly reduced. These results indicate limited mice. streptozotocin (STZ)-induced model mice alterations (but serine) at week after elevated disposal confirmed co-administration weeks injection. both contribute acceleration catabolism circulating Of note, weight gain high-fat diet (HFD) attenuated dietary restriction fat mass treatment HFD alone, food, calorie, water intake; calorie absorption; tolerance; physical activity all unaffected. Recent reports suggest microbiome composition gut neuropathy5. Investigation fecal log ratios strains microorganisms expressing complete biosynthesis while pathways pathway serine- glycine-restricted HFD. Serine sphingolipid via palmitoyl transferase. Sphingolipids abundantly contained myelin sheath nerves. Restriction palmitate 70% serine-replete control diets. Hepatic cholesterol serine-free group group, enzymes an increase no change enzymes. Recently, nerves proinflammatory macrophage infiltration activated RAGE signaling deficits retrograde axonal transportation. less B phosphorylation than carbohydrate contents, could evoke independent signaling. various neurodegenerative disorders previous clinical studies. Similarly, fed glycine-free low-fat chow diets 12 months exhibited thermal hypoalgesia intraepidermal paw skin. Interestingly, accelerated just 3 months. findings low systemic feeding accelerates authors further explored restriction. 1-Deoxysphingolipids, deoxydihydroceramides, neurotoxic sphingolipids. 1-deoxysphingolipid produced when enzyme biosynthetic palmitoyltransferase, uses l-alanine substrate instead canonical substrate, serine. expected, contents deoxydihydro-ceramides liver skin HFD, ceramide content Administration inhibitor transferase (myriocin) strongly sphingolipids triglycerides diacylglycerides. Myriocin ameliorated density myriocin had impact tactile sensing conduction velocities. Importantly, administration 6 age prevented manifestation sensation, without affecting body gain, levels. Myriosin effects 1-deoxysphingolipids ceramides. Finally, based obtained thus far, investigated whether serine-supplemented prevents 3% serine-enriched starting serine, comparable, slight observed. Neuropathic manifestations, diet. Canonical similar across tissues, robustly Collectively, data prevent progression novel point research correcting intake blood Currently, radical therapy established. aldose reductase inhibitors α-lipoic clinically applied, limited. This study suggests due insufficient action insulin. important itself, may necessary consider focus improving more organs. nutrient factors lipids will accelerate explains one reasons why cannot suppressed alone. Conversely, some extent, completely report. reconfirm multifactorial disease. Therefore, conceivable administered adjunctive control. Unfortunately, relate prevention administration, they do constitute treatment. future, evaluate alleviate already developed progressed confirm efficacy prospective research.

Language: Английский

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