Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Язык: Английский

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The role of gut microbiota in cancer treatment: friend or foe?

Gut, Год журнала: 2020, Номер 69(10), С. 1867 - 1876

Опубликована: Авг. 5, 2020

The gut microbiota has been implicated in cancer and shown to modulate anticancer drug efficacy. Altered is associated with resistance chemo drugs or immune checkpoint inhibitors (ICIs), whereas supplementation of distinct bacterial species restores responses the drugs. Accumulating evidence revealed potential modulating enhance efficacy Regardless valuable findings by preclinical models clinical data patients cancer, a more thorough understanding interactions therapy helps researchers identify novel strategy for prevention, stratify effective treatment reduce complication. In this review, we discuss scientific on role treatment, highlight latest knowledge technologies leveraged target specific bacteria that contribute tumourigenesis. First, provide an overview establishing links between bacteria, inflammation treatment. Second, mechanisms used growth, responses, as well chemotherapeutic ICIs. Third, demonstrate various approaches their translational research. Finally, limitations current microbiome research context ongoing efforts overcome these challenges future perspectives.

Язык: Английский

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The gut microbiome: an orchestrator of xenobiotic metabolism

Acta Pharmaceutica Sinica B, Год журнала: 2019, Номер 10(1), С. 19 - 32

Опубликована: Дек. 10, 2019

Microbes inhabiting the intestinal tract of humans represent a site for xenobiotic metabolism. The gut microbiome, collection microorganisms in gastrointestinal tract, can alter metabolic outcome pharmaceuticals, environmental toxicants, and heavy metals, thereby changing their pharmacokinetics. Direct chemical modification xenobiotics by either through or re-entering via enterohepatic circulation, lead to increased metabolism bioactivation, depending on enzymatic activity within microbial niche. Unique enzymes encoded microbiome include those that reverse modifications imparted host detoxification pathways. Additionally, limit absorption small intestine increasing expression cell–cell adhesion proteins, supporting protective mucosal layer, and/or directly sequestering chemicals. Lastly, gene is regulated including CYP450s, multi-drug resistance transcription factors regulate them. While affects pharmacokinetics xenobiotic, also influence viability microbiome. Our understanding complex interconnectedness between host, will advance with new modeling systems, technology development refinement, mechanistic studies focused contribution human

Язык: Английский

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Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease

mSystems, Год журнала: 2020, Номер 5(5)

Опубликована: Сен. 14, 2020

Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates misfolded alpha-synuclein along cerebral axis. Several studies report association between intestinal dysbiosis and disease, although cause-effect relationship remains to be established. Herein, gut microbiota composition 64 Italian patients with 51 controls was determined using next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry also investigated. The most significant changes within group highlighted reduction in bacterial taxa, which are linked anti-inflammatory/neuroprotective effects, particularly Lachnospiraceae family key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, Blautia direct evaluation fecal metabolites revealed several classes metabolites. Changes were seen lipids (linoleic acid, oleic succinic sebacic acid), vitamins (pantothenic acid nicotinic amino acids (isoleucine, leucine, phenylalanine, glutamic pyroglutamic acid) other organic compounds (cadaverine, ethanolamine, hydroxy propionic acid). Most modified strongly correlated abundance members belonging family, suggesting that these bacteria correlate altered metabolism rates disease.IMPORTANCE To our knowledge, this one few thus far correlates analysis disease. Overall, data highlight modifications numerous This suggests associated dysregulation involves synergistic microbes favoring homeostasis. Interestingly, short-chain fatty (SCFA)-producing influenced metabolomics profile, affecting potential protective effects Parkinson group. On hand, extensive impact has at level metabolic pathways could encourage identification specific biomarkers for diagnosis treatment light effect drugs have microbiota.

Язык: Английский

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Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics: An UNGAP review

European Journal of Pharmaceutical Sciences, Год журнала: 2021, Номер 162, С. 105812 - 105812

Опубликована: Март 20, 2021

The absorption of oral drugs is frequently plagued by significant variability with potentially serious therapeutic consequences. source can be traced back to interindividual in physiology, differences special populations (age- and disease-dependent), drug formulation properties, or food-drug interactions. Clinical evidence for the impact some these factors on pharmacokinetic mounting: e.g. gastric pH emptying time, small intestinal fluid pediatrics elderly, surgical changes gastrointestinal anatomy. However, link colonic (transit composition, microbiome), sex (male vs. female) gut-related diseases (chronic constipation, anorexia cachexia) has not been firmly established yet. At same a way decrease provided pharmaceutical industry: clinical suggests that approaches employed during development exposure. This review outlines main drivers exposure potential overcome them, while highlighting existing knowledge gaps guiding future studies this area.

Язык: Английский

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Where to Look into the Puzzle of Polyphenols and Health? The Postbiotics and Gut Microbiota Associated with Human Metabotypes

Molecular Nutrition & Food Research, Год журнала: 2020, Номер 64(9)

Опубликована: Март 20, 2020

Abstract The full consensus on the role of dietary polyphenols as human‐health‐promoting compounds remains elusive. two‐way interaction between and gut microbiota (GM) (i.e., modulation GM by their catabolism GM) is determinant in polyphenols’ effects. identification human metabotypes associated with a differential microbial metabolism has opened new research scenarios to explain inter‐individual variability upon consumption. unequivocally identified so far are those involved isoflavones (equol and(or) O ‐desmethylangolesin producers versus non‐producers) ellagic acid (urolithin metabotypes, including only urolithin‐A (UM‐A), urolithin‐A, isourolithin‐A, urolithin‐B (UM‐B), non‐producers (UM‐0)). In addition, metabolites (phenolic‐derived postbiotics) such equol, urolithins, valerolactones, enterolactone, enterodiol, 8‐prenylnaringenin, among others, can exert health knowledge updated position taken here i) polyphenols, ii) evidence phenolic‐derived postbiotics health, iii) biomarkers clustering individuals depending (metabotyping) effects, iv) catecholamines illustrate intersection personalized nutrition precision medicine.

Язык: Английский

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Gut Bacteria and Neurotransmitters

Microorganisms, Год журнала: 2022, Номер 10(9), С. 1838 - 1838

Опубликована: Сен. 14, 2022

Gut bacteria play an important role in the digestion of food, immune activation, and regulation entero-endocrine signaling pathways, but also communicate with central nervous system (CNS) through production specific metabolic compounds, e.g., bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin (5-HT) histamine. Afferent vagus nerve (VN) fibers that transport signals from gastro-intestinal tract (GIT) gut microbiota to brain are linked receptors esophagus, liver, pancreas. In response these stimuli, sends back entero-epithelial cells via efferent VN fibers. Fibers not direct contact wall or intestinal microbiota. Instead, reach 100 500 million neurons enteric (ENS) submucosa myenteric plexus wall. The modulation, development, renewal ENS controlled by microbiota, especially those ability produce metabolize hormones. Signals generated hypothalamus pituitary adrenal glands hypothalamic axis (HPA). SCFAs produced adhere free (FFARs) on surface epithelial (IECs) interact enter circulatory system. alter synthesis degradation neurotransmitters. This review focuses effect have neurotransmitters vice versa.

Язык: Английский

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Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level

Cell Host & Microbe, Год журнала: 2020, Номер 28(2), С. 245 - 257.e6

Опубликована: Июнь 15, 2020

Язык: Английский

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The microbiome–gut–brain axis in Parkinson disease — from basic research to the clinic

Nature Reviews Neurology, Год журнала: 2022, Номер 18(8), С. 476 - 495

Опубликована: Июнь 24, 2022

Язык: Английский

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Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Фев. 24, 2021

Abstract The phenylalanine–tyrosine–dopa–dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is rate-limiting enzyme that hydroxylates and generates levodopa ( l -dopa) with tetrahydrobiopterin (BH 4 ) as a coenzyme. Here, we show oral berberine (BBR) might supply H • through dihydroberberine (reduced BBR produced by bacterial nitroreductase) promote production of BH from dihydrobiopterin; increased enhances TH activity, which accelerates -dopa gut bacteria. Oral acts in way similar vitamins. intestinal bacteria enters brain circulation transformed dopamine. To verify gut–brain dialog activated BBR’s effect, Enterococcus faecalis or faecium was transplanted into Parkinson’s disease (PD) mice. significantly ameliorated PD manifestation mice; additionally, combination showed better therapeutic effect than alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging identified elevated striatal levels mouse brains , strengthened intensity These results demonstrated an agonist could lead gut. Furthermore, study 28 patients hyperlipidemia confirmed blood/fecal Hence, improve function upregulating biosynthesis microbiota vitamin-like effect.

Язык: Английский

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