bims-metalz 2023-10-01 papers

bims-metalz

Biomed News

on Metabolic causes of Alzheimer’s disease

Issue of 2023–10–01
eight papers selected by
Mikaila Chetty, Goa University

Biochemical and Molecular Pathways in Neurodegenerative Diseases: An Integrated View.
Oh my gut! Is the microbial origin of neurodegenerative diseases real?
Gut-muscle-brain axis: Molecular mechanisms in neurodegenerative disorders and potential therapeutic efficacy of probiotic supplementation coupled with exercise.
Diet-gut microbiome interaction and ferulic acid bioavailability: implications on neurodegenerative disorders.
The impact of Parkinson's disease-associated gut microbiota on the transcriptome in Drosophila.
Editorial: Microbiome metabolites in health and disease.
Mitochondria of intestinal epithelial cells in depression: Are they at a crossroads of gut-brain communication?
Human gut microbiome: Therapeutic opportunities for metabolic syndrome-Hype or hope?

Cells. 2023 Sep 20. pii: 2318. [Epub ahead of print]12(18):

Biochemical and Molecular Pathways in Neurodegenerative Diseases: An Integrated View.

Nitesh Sanghai, Geoffrey K Tranmer.

  Neurodegenerative diseases (NDDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are defined by a myriad of complex aetiologies. Understanding the common biochemical molecular pathologies among NDDs gives an opportunity to decipher the overlapping and numerous cross-talk mechanisms of neurodegeneration. Numerous interrelated pathways lead to the progression of neurodegeneration. We present evidence from the past pieces of literature for the most usual global convergent hallmarks like ageing, oxidative stress, excitotoxicity-induced calcium butterfly effect, defective proteostasis including chaperones, autophagy, mitophagy, and proteosome networks, and neuroinflammation. Herein, we applied a holistic approach to identify and represent the shared mechanism across NDDs. Further, we believe that this approach could be helpful in identifying key modulators across NDDs, with a particular focus on AD, PD, and ALS. Moreover, these concepts could be applied to the development and diagnosis of novel strategies for diverse NDDs.

Keywords:  Alzheimer’s disease; Parkinson’s disease; ageing; amyotrophic lateral sclerosis; autophagy; calcium butterfly effect; chaperones; excitotoxicity; mitophagy; neurodegenerative diseases; neuroinflammation; oxidative stress; proteostasis

DOI:  https://doi.org/10.3390/cells12182318
Infect Immun. 2023 Sep 26. e0043722

Oh my gut! Is the microbial origin of neurodegenerative diseases real?

Alyssa Walker, Daniel M Czyz.

  There is no cure or effective treatment for neurodegenerative protein conformational diseases (PCDs), such as Alzheimer's or Parkinson's diseases, mainly because the etiology of these diseases remains elusive. Recent data suggest that unique changes in the gut microbial composition are associated with these ailments; however, our current understanding of the bacterial role in the pathogenesis of PCDs is hindered by the complexity of the microbial communities associated with specific microbiomes, such as the gut, oral, or vaginal microbiota. The composition of these specific microbiomes is regarded as a unique fingerprint affected by factors such as infections, diet, lifestyle, and antibiotics. All of these factors also affect the severity of neurodegenerative diseases. The majority of studies that reveal microbial contribution are correlational, and various models, including worm, fly, and mouse, are being utilized to decipher the role of individual microbes that may affect disease onset and progression. Recent evidence from across model organisms and humans shows a positive correlation between the presence of gram-negative enteropathogenic bacteria and the pathogenesis of PCDs. While these correlational studies do not provide a mechanistic explanation, they do reveal contributing bacterial species and provide an important basis for further investigation. One of the lurking concerns related to the microbial contribution to PCDs is the increasing prevalence of antibiotic resistance and poor antibiotic stewardship, which ultimately select for proteotoxic bacteria, especially the gram-negative species that are known for intrinsic resistance. In this review, we summarize what is known about individual microbial contribution to PCDs and the potential impact of increasing antimicrobial resistance.

Keywords:  Alzheimer's disease; Caenorhabditis elegans; Parkinson's disease; human gut microbiota; neurodegenerative diseases; protein conformational diseases; proteostasis

DOI:  https://doi.org/10.1128/iai.00437-22
Neuropharmacology. 2023 Sep 27. pii: S0028-3908(23)00308-8. [Epub ahead of print] 109718

Gut-muscle-brain axis: Molecular mechanisms in neurodegenerative disorders and potential therapeutic efficacy of probiotic supplementation coupled with exercise.

Ilaria Morella, Massimo Negro, Maurizia Dossena, Riccardo Brambilla, Giuseppe D'Antona.

Increased longevity is often associated with age-related conditions. The most common neurodegenerative disorders in the older population are Alzheimer's disease (AD) and Parkinson's disease (PD), associated with progressive neuronal loss leading to functional and cognitive impairments. Although symptomatic treatments are available, there is currently no cure for these conditions. Gut dysbiosis has been involved in the pathogenesis of AD and PD, thus interventions targeting the "gut-brain axis" could potentially prevent or delay these pathologies. Recent evidence suggests that the skeletal muscle and the gut microbiota can affect each other via the "gut-muscle axis". Importantly, cognitive functions in AD and PD patients significantly benefit from physical activity. In this review, we aim to provide a comprehensive picture of the crosstalk between the brain, the skeletal muscle and the gut microbiota, introducing the concept of "gut-muscle-brain axis". Moreover, we discuss human and animal studies exploring the modulatory role of exercise and probiotics on cognition in AD and PD. Collectively, the findings presented here support the potential benefits of physical activity and probiotic supplementation in AD and PD. Further studies will be needed to develop targeted and multimodal strategies, including lifestyle changes, to prevent or delay the course of these pathologies.

DOI: https://doi.org/10.1016/j.neuropharm.2023.109718
Eur J Nutr. 2023 Sep 25.

Diet-gut microbiome interaction and ferulic acid bioavailability: implications on neurodegenerative disorders.

Saarika Pothuvan Kunnummal, Mahejibin Khan.

   PURPOSE OF THE REVIEW: Ferulic acid (FA), which occurs naturally as the feruloylated sugar ester in grains, fruits, and vegetables, is critical for combating oxidative stress and alleviating neurodegenerative diseases resulting from free radical-generated protein aggregates in brain cells. However, FA cannot be absorbed in conjugated form. Therefore, strategies to improve the bioavailability of FA are gaining more importance. Ferulic acid esterases (FAE) of the gut microbiota are critical enzymes that facilitate FA release from feruloylated sugar ester conjugates and influence systemic health. This review provides insight into a nutrition-based approach to preventing neurodegenerative disorders such as Alzheimer's and Parkinson's by altering the diversity of FAE-producing gut microbiota.
RECENT FINDINGS: The human gut is a niche for a highly dense microbial population. Nutrient components and the quality of food shape the gut microbiota. Microbiota-diet-host interaction primarily involves an array of enzymes that hydrolyse complex polysaccharides and release covalently attached moieties, thereby increasing their bio-accessibility. Moreover, genes encoding polysaccharide degrading enzymes are substrate inducible, giving selective microorganisms a competitive advantage in scavenging nutrients. Nutraceutical therapy using specific food components holds promise as a prophylactic agent and as an adjunctive treatment strategy in neurotherapeutics, as it results in upregulation of polysaccharide utilisation loci containing fae genes in the gut microbiota, thereby increasing the release of FA and other antioxidant molecules and combat neurodegenerative processes.

Keywords:  Ferulic acid; Feruloyl esterases; Gut microbial diversity; Neurological disorders; Nutritional intervention; Polysaccharide utilisation loci

DOI:  https://doi.org/10.1007/s00394-023-03247-0
Microbiol Spectr. 2023 Sep 27. e0017623

The impact of Parkinson's disease-associated gut microbiota on the transcriptome in Drosophila.

Xin Liu, Meng Yang, Runzhou Liu, Fan Zhou, Haibing Zhu, Xiaoyun Wang.

  Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people, and many studies have confirmed that the disorder of gut microbiota is involved in the pathophysiological process of PD. However, the molecular mechanism of gut microbiota in regulating the pathogenesis of PD is still lacking. In this study, to investigate the impact of PD-associated gut microbiota on host transcriptome, we established various PD models with fecal microbiota transplantation (FMT) in the model organism Drosophila followed by integrative data analysis of microbiome and transcriptome. We first constructed rotenone-induced PD models in Drosophila followed by FMT in different groups. Microbial analysis by 16S rDNA sequencing showed that gut microbiota from PD Drosophila could affect bacterial structure of normal Drosophila, and gut microbiota from normal Drosophila could affect bacterial structure of PD Drosophila. Transcriptome analysis revealed that PD-associated gut microbiota influenced expression patterns of genes enriched in neuroactive ligand-receptor interaction, lysosome, and diverse metabolic pathways. Importantly, to verify our findings, we transplanted Drosophila with fecal samples from clinical PD patients. Compared to the control, Drosophila transplanted with fecal samples from PD patients had reduced microbiota Acetobacter and Lactobacillus, and differentially expressed genes enriched in diverse metabolic pathways. In summary, our results reveal the influence of PD-associated gut microbiota on host gene expression, and this study can help better understand the link between gut microbiota and PD pathogenesis through gut-brain axis. IMPORTANCE Gut microbiota plays important roles in regulating host gene expression and physiology through complex mechanisms. Recently, it has been suggested that disorder of gut microbiota is involved in the pathophysiological process of Parkinson's disease (PD). However, the molecular mechanism of gut microbiota in regulating the pathogenesis of PD is still lacking. In this study, to investigate the impact of PD-associated gut microbiota on host transcriptome, we established various PD models with fecal microbiota transplantation in the model organism Drosophila followed by integrative data analysis of microbiome and transcriptome. We also verified our findings by transplanting Drosophila with fecal samples from clinical PD patients. Our results demonstrated that PD-associated gut microbiota can induce differentially expressed genes enriched in diverse metabolic pathways. This study can help better understand the link between gut microbiota and PD pathogenesis through gut-brain axis.

Keywords:  Drosophila melanogaster; Parkinson’s disease; fecal microbiota transplantation; gut microbiota; transcriptome

DOI:  https://doi.org/10.1128/spectrum.00176-23
Front Microbiol. 2023 ;14 1270001

Editorial: Microbiome metabolites in health and disease.

Emanuel E Canfora, Mark A Feitelson, Alla Arzumanyan.



Keywords:  acute liver failure (ALF); celiac disease; gut barrier function; microbial metabolites; sepsis; short chain fatty acids

DOI:  https://doi.org/10.3389/fmicb.2023.1270001
Neurosci Biobehav Rev. 2023 Sep 22. pii: S0149-7634(23)00372-X. [Epub ahead of print]153 105403

Mitochondria of intestinal epithelial cells in depression: Are they at a crossroads of gut-brain communication?

Yi Wang, Han Lai, Tian Zhang, Jing Wu, Huiling Tang, Xuanwei Liang, Dandan Ren, Jinzhu Huang, Weihong Li.

  The role of gut dysbiosis in depression is well established. However, recent studies have shown that gut microbiota is regulated by intestinal epithelial cell (IEC) mitochondria, which has yet to receive much attention. This review summarizes the recent developments about the critical role of IEC mitochondria in actively maintaining gut microbiota, intestinal metabolism, and immune homeostasis. We propose that IEC mitochondrial dysfunction alters gut microbiota composition, participates in cell fate, mediates oxidative stress, activates the peripheral immune system, causes peripheral inflammation, and transmits peripheral signals through the vagus and enteric nervous systems. These pathological alterations lead to brain inflammation, disruption of the blood-brain barrier, activation of the hypothalamic-pituitary-adrenal axis, activation of microglia and astrocytes, induction of neuronal loss, and ultimately depression. Furthermore, we highlight the prospect of treating depression through the mitochondria of IECs. These new findings suggest that the mitochondria of IECs may be a newly found important factor in the pathogenesis of depression and represent a potential new strategy for treating depression.

Keywords:  Depression; Gut microbiota; Gut-brain axis; Intestinal epithelial cells; Mitochondria

DOI:  https://doi.org/10.1016/j.neubiorev.2023.105403
Endocrinol Diabetes Metab. 2023 Sep 28. e436

Human gut microbiome: Therapeutic opportunities for metabolic syndrome-Hype or hope?

Angela Horvath, Kristina Zukauskaite, Olha Hazia, Irina Balazs, Vanessa Stadlbauer.

  Shifts in gut microbiome composition and metabolic disorders are associated with one another. Clinical studies and experimental data suggest a causal relationship, making the gut microbiome an attractive therapeutic goal. Diet, intake of probiotics or prebiotics and faecal microbiome transplantation (FMT) are methods to alter a person's microbiome composition. Although FMT may allow establishing a proof of concept to use microbiome modulation to treat metabolic disorders, studies show mixed results regarding the effects on metabolic parameters as well as on the composition of the microbiome. This review summarizes the current knowledge on diet, probiotics, prebiotics and FMT to treat metabolic diseases, focusing on studies that also report alterations in microbiome composition. Furthermore, clinical trial results on the effects of common drugs used to treat metabolic diseases are synopsized to highlight the bidirectional relationship between the microbiome and metabolic diseases. In conclusion, there is clear evidence that microbiome modulation has the potential to influence metabolic diseases; however, it is not possible to distinguish which intervention is the most successful. In addition, a clear commitment from all stakeholders is necessary to move forward in the direction of developing targeted interventions for microbiome modulation.

Keywords:  diet; faecal microbiota transplantation; metabolic syndrome; microbiome; obesity; prebiotic; probiotic

DOI:  https://doi.org/10.1002/edm2.436