Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine

Gut Microbes, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 12, 2025

The therapeutic benefits of opioids are compromised by the development analgesic tolerance, which necessitates higher dosing for pain management thereby increasing liability drug dependence and addiction. Rodent models indicate opposing roles gut microbiota in tolerance: morphine-induced dysbiosis exacerbates whereas probiotics ameliorate tolerance. Not all individuals develop could be influenced differences microbiota, yet no study design has capitalized upon this natural variation. We leveraged behavioral variation a murine model voluntary oral morphine self-administration to elucidate mechanisms influences Although mice shared similar morphine-driven changes that largely masked informative associations with variability our high-resolution temporal analyses revealed divergence progression best explained sustained antinociception. Mice did not tolerance maintained capacity production short-chain fatty acid (SCFA) butyrate known bolster intestinal barriers promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor dietary supplementation significantly reduced independently suppression systemic inflammation. These findings inform immediate therapies extend efficacy opioids.

Язык: Английский

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The impact of gut microbiota on the occurrence, treatment, and prognosis of ischemic stroke

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106836 - 106836

Опубликована: Фев. 1, 2025

Ischemic stroke (IS) is a cerebrovascular disease that predominantly affects middle-aged and elderly populations, exhibiting high mortality disability rates. At present, the incidence of IS increasing annually, with notable trend towards younger affected individuals. Recent discoveries concerning "gut-brain axis" have established connection between gut brain. Numerous studies revealed intestinal microbes play crucial role in onset, progression, outcomes IS. They are involved entire pathophysiological process through mechanisms such as chronic inflammation, neural regulation, metabolic processes. Although numerous explored relationship microbiota, comprehensive analyses specific microbiota relatively scarce. Therefore, this paper provides an overview typical changes following investigates microorganisms context. Additionally, it presents analysis post-stroke microbiological therapy diet. The aim to identify potential microbial targets for therapeutic intervention, well highlight benefits therapies significance dietary management. Overall, seeks provide key strategies treatment management IS, advocating healthy diets health programs Meanwhile, may offer new perspective on future interdisciplinary development neurology, microbiology nutrition.

Язык: Английский

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Dietary whey protein protects against Crohn’s disease by orchestrating cross-kingdom interaction between the gut phageome and bacteriome

Gut, Год журнала: 2025, Номер unknown, С. gutjnl - 334516

Опубликована: Март 23, 2025

Background The gut microbiome and diet are important factors in the pathogenesis management of Crohn’s disease (CD). However, role phageome under dietary influences is unknown. Objective We aim to explore effect on phageome-bacteriome interaction linking CD protection. Design recruited patients healthy subjects (n=140) conducted a multiomics investigation, including paired ileal mucosa bacteriome profiling, survey phenome interrogation. screened for bacteriome, as well its epidemiological association with risks. underlying mechanisms were explored target phage-bacteria monocultures cocultures vitro two mouse models vivo. Results On screening humans, whey protein (WP) consumption was found profoundly impact (more pronounced phageome) associated lower risk. Indeed, WP reshaped can causally attenuate intestinal inflammation, shown by faecal versus transplantation from WP-consuming WP-non-consuming mice recipient mice. Mechanistically, induced phage (a newly isolated AkkZT003P herein) lysis mucin-foraging bacterium Akkermansia muciniphila , which unleashed symbiotic Streptococcus thermophilus counteract inflammation. Conclusion Our study charted importance cross-kingdom between bacteria mediating Importantly, we uncovered beneficial WP, keystone AkkZT003P, probiotic S. that be used future.

Язык: Английский

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Impact of Microbiome–Brain Communication on Neuroinflammation and Neurodegeneration

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14925 - 14925

Опубликована: Окт. 5, 2023

The gut microbiome plays a pivotal role in maintaining human health, with numerous studies demonstrating that alterations microbial compositions can significantly affect the development and progression of various immune-mediated diseases affecting both digestive tract central nervous system (CNS). This complex interplay between microbiota, gut, CNS is referred to as gut-brain axis. microbiota pathogenesis neurodegenerative has gained increasing attention recent years, evidence suggests dysbiosis may contribute disease progression. Clinical have shown composition multiple sclerosis patients, decrease beneficial bacteria an increase pro-inflammatory bacteria. Furthermore, changes within community been linked Parkinson's Alzheimer's disease. Microbiota-gut-brain communication impact through mechanisms, including regulation immune function, production metabolites, well modulation host-derived soluble factors. review describes current literature on axis highlights novel systems allow cross-talk host might influence neuroinflammation neurodegeneration.

Язык: Английский

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Akkermansia muciniphila - friend or foe in colorectal cancer?

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Дек. 6, 2023

Akkermansia muciniphila is a gram-negative anaerobic bacterium, which represents part of the commensal human microbiota. Decline in abundance A. among other microbial species gut correlates with severe systemic diseases such as diabetes, obesity, intestinal inflammation and colorectal cancer. Due to its mucin-reducing immunomodulatory properties, use probiotics containing sp. appears promising approach treatment metabolic inflammatory diseases. In particular, number studies have focused on role Of note, results these mice are contradictory: some reported protective cancer, while others demonstrated that administration could aggravate course disease resulting increased tumor burden. More recent suggested effect certain unique surface antigens immune system. this Perspective, we attempt explain how contributes protection against cancer models, being pathogenic others. We argue differences experimental protocols , well viability bacteria, may significantly affect results. addition, hypothesize presented by pasteurized bacteria or live exert distinct effects barrier functions gut. Finally, reduce mucin exerts combined bacterial either promoting inhibiting development.

Язык: Английский

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A High-Fat, High-Cholesterol Diet Promotes Intestinal Inflammation by Exacerbating Gut Microbiome Dysbiosis and Bile Acid Disorders in Cholecystectomy

Nutrients, Год журнала: 2023, Номер 15(17), С. 3829 - 3829

Опубликована: Сен. 1, 2023

Patients with post-cholecystectomy (PC) often experience adverse gastrointestinal conditions, such as PC syndrome, colorectal cancer (CRC), and non-alcoholic fatty liver disease (NAFLD), that accumulate over time. An epidemiological survey further revealed the risk of cholecystectomy is associated high-fat high-cholesterol (HFHC) dietary intake. Mounting evidence suggests disrupted gut microbial homeostasis dysregulated bile acids (BAs) metabolism. However, effect an HFHC diet on complications after has not been elucidated. Here, we aimed to investigate microbiota–BA metabolic axis elucidate association between this alteration development intestinal inflammation. In study, a mice model was established, levels IL-Iβ, TNF-α, IL-6 in colon were increased fed for 6 weeks. Analysis fecal BA metabolism showed altered rhythm by upregulating CPY7A1, CYP8B1, BSEP ileal ASBT mRNA expression levels, resulting levels. addition, feeding caused significant dysbiosis microbiota, which characterized enrichment microbiota involved BAs; abundance pro-inflammatory related metabolite also significantly higher. contrast, major short-chain acid (SCFA)-producing bacteria decreased. Overall, our study promotes inflammation exacerbating microbiome cholecystectomy. Our provides useful insights into maintenance health through or probiotic intervention strategies.

Язык: Английский

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The role of morphine‐ and fentanyl‐induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota‐gut‐brain axis

The FASEB Journal, Год журнала: 2024, Номер 38(8)

Опубликована: Апрель 22, 2024

Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes dysbiosis. Depleting gut bacteria can preclude development of tolerance opioid-induced antinociception, suggesting an important role gut-brain axis in mediating effects. The mechanism underlying dysbiosis, however, remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for integrity barrier they prevent pathogenesis enteric microbiota. Here, we report or fentanyl reduces activity ileum, resulting changes composition bacteria. Fecal samples from morphine-treated mice had increased levels Akkermansia muciniphila with a shift abundance ratio Firmicutes Bacteroidetes. microbial transplant (FMT) morphine-naïve oral supplementation butyrate restored (a) activity, (b) expression peptide, Reg3γ, (c) prevented increase permeability (d) antinociceptive morphine-dependent mice. Improved function FMT enrichment mucin-degrading A. These data implicate impairment epithelium by which opioids disrupt microbiota-gut-brain axis.

Язык: Английский

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A history of repeated antibiotic usage leads to microbiota-dependent mucus defects

Gut Microbes, Год журнала: 2024, Номер 16(1)

Опубликована: Июль 21, 2024

Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and ultimately changes the gut microbiota community. However, physiological effects of - but not recent on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from deeply phenotyped Estonian Microbiome Cohort (EstMB), we here utilized human-to-mouse fecal transplantation to explore long-term impacts use intestinal mucus function. While a healthy layer protects epithelium against infection inflammation, using

Язык: Английский

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Difference in gut microbial dysbiotic patterns between body-first and brain-first Parkinson's disease

Neurobiology of Disease, Год журнала: 2024, Номер 201, С. 106655 - 106655

Опубликована: Авг. 30, 2024

This study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes Parkinson's disease (PD). could illuminate the unique pathogenic mechanisms within these subtypes.

Язык: Английский

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Macleaya cordata isoquinoline alkaloids attenuate Escherichia coli lipopolysaccharide-induced intestinal epithelium injury in broiler chickens by co-regulating the TLR4/MyD88/NF-κB and Nrf2 signaling pathways

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 17, 2024

This study sought to explore the effects and potential mechanisms of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata alleviate lipopolysaccharide (LPS)-induced intestinal epithelium injury in broilers. A total 486 1-day-old broilers were assigned at random a control (CON) group, LPS LPS+IA group 21-d study. The CON groups received basal diet, while diet supplemented 0.6 mg/kg IA. At 17, 19, 21 days age, LPS+BP injected intraperitoneally LPS, was equivalent amount saline solution. results manifested that injection caused inflammation lipid peroxidation, disrupted barrier function, increased abundance harmful microorganisms. However, IA alleviated LPS-induced adverse changes morphology, apoptosis, mucosal integrity, cecum microorganisms, homeostasis disorder by decreasing inflammatory cytokines enhancing antioxidant-related genes expressions; inhibited increases TLR4 NF-κB expressions decreases Nrf2 GPX1 expressions. Our findings indicated addition attenuated anti-inflammatory antioxidant capacity broiler chickens possibly via co-regulating TLR4/MyD88/NF-κB signaling pathways.

Язык: Английский

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