scholarly journals The gut-microbiota-brain axis in autism: what Drosophila models can offer?

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Safa Salim ◽  
Ayesha Banu ◽  
Amira Alwa ◽  
Swetha B. M. Gowda ◽  
Farhan Mohammad

AbstractThe idea that alterations in gut-microbiome-brain axis (GUMBA)-mediated communication play a crucial role in human brain disorders like autism remains a topic of intensive research in various labs. Gastrointestinal issues are a common comorbidity in patients with autism spectrum disorder (ASD). Although gut microbiome and microbial metabolites have been implicated in the etiology of ASD, the underlying molecular mechanism remains largely unknown. In this review, we have summarized recent findings in human and animal models highlighting the role of the gut-brain axis in ASD. We have discussed genetic and neurobehavioral characteristics of Drosophila as an animal model to study the role of GUMBA in ASD. The utility of Drosophila fruit flies as an amenable genetic tool, combined with axenic and gnotobiotic approaches, and availability of transgenic flies may reveal mechanistic insight into gut-microbiota-brain interactions and the impact of its alteration on behaviors relevant to neurological disorders like ASD.

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2277
Author(s):  
Paulina Pawelec ◽  
Malgorzata Ziemka-Nalecz ◽  
Joanna Sypecka ◽  
Teresa Zalewska

Fractalkine (FKN, CX3CL1) is a transmembrane chemokine expressed by neurons in the central nervous system (CNS). CX3CL1 signals through its unique receptor, CX3CR1, that is expressed in microglia. Within the CNS, fractalkine acts as a regulator of microglia activation in response to brain injury or inflammation. During the last decade, there has been a growing interest in the roles that the CX3CL1/CX3CR1 signaling pathway plays in the neuropathology of a diverse array of brain disorders. However, the reported results have proven controversial, indicating that a disruption of the CX3CL1 axis induces a disease-specific microglial response that may have either beneficial or detrimental effects. Therefore, it has become clear that the understanding of neuron-to-glia signals mediated by CX3CL1/CX3CR1 at different stages of diseases could provide new insight into potential therapeutic targets. Hence, the aim of this review is to provide a summary of the literature on the emerging role of CX3CL1 in animal models of some brain disorders.


2022 ◽  
Vol 8 ◽  
Author(s):  
Shuangyue Li ◽  
Georgios Kararigas

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maike Willers ◽  
Dorothee Viemann

Abstract Colonization of the intestine with commensal bacteria is known to play a major role in the maintenance of human health. An altered gut microbiome is associated with various ensuing diseases including respiratory diseases. Here, we summarize current knowledge on the impact of the gut microbiota on airway immunity with a focus on consequences for the host defense against respiratory infections. Specific gut commensal microbiota compositions and functions are depicted that mediate protection against respiratory infections with bacterial and viral pathogens. Lastly, we highlight factors that have imprinting effects on the establishment of the gut microbiota early in life and are potentially relevant in the context of respiratory infections. Deepening our understanding of these relationships will allow to exploit the knowledge on how gut microbiome maturation needs to be modulated to ensure lifelong enhanced resistance towards respiratory infections.


Author(s):  
Ghada Araji ◽  
Julian Maamari ◽  
Fatima Ali Ahmad ◽  
Rana Zareef ◽  
Patrick Chaftari ◽  
...  

ABSTRACT The discovery of immune checkpoint inhibitors (ICIs) has revolutionized the care of cancer patients. However, the response to ICI therapy exhibits substantial interindividual variability. Efforts have been directed to identify biomarkers that predict the clinical response to ICIs. In recent years, the gut microbiome has emerged as a critical player that influences the efficacy of immunotherapy. An increasing number of studies have suggested that the baseline composition of a patient's gut microbiota and its dysbiosis are correlated with the outcome of cancer immunotherapy. This review tackles the rapidly growing body of evidence evaluating the relationship between the gut microbiome and the response to ICI therapy. Additionally, this review highlights the impact of antibiotic-induced dysbiosis on ICI efficacy and discusses the possible therapeutic interventions to optimize the gut microbiota composition to augment immunotherapy efficacy.


2020 ◽  
Vol 7 ◽  
Author(s):  
Liv R. Dedon ◽  
Ezgi Özcan ◽  
Asha Rani ◽  
David A. Sela

Human milk oligosaccharides (HMOs) enrich beneficial bifidobacteria in the infant gut microbiome which produce molecules that impact development and physiology. 2′fucosyllactose (2′FL) is a highly abundant fucosylated HMO which is utilized by Bifidobacterium longum subsp. infantis, despite limited scientific understanding of the underlying mechanism. Moreover, there is not a current consensus on whether free fucose could be metabolized when not incorporated in a larger oligosaccharide structure. Based on metabolic and genomic analyses, we hypothesize that B. infantis catabolizes both free fucose and fucosyl oligosaccharide residues to produce 1,2-propanediol (1,2-PD). Accordingly, systems-level approaches including transcriptomics and proteomics support this metabolic path. Co-fermentation of fucose and limiting lactose or glucose was found to promote significantly higher biomass and 1,2-PD concentrations than individual substrates, suggesting a synergistic effect. In addition, and during growth on 2′FL, B. infantis achieves significantly higher biomass corresponding to increased 1,2-PD. These findings support a singular fucose catabolic pathway in B. infantis that is active on both free and HMO-derived fucose and intimately linked with central metabolism. The impact of fucose and 2′FL metabolism on B. infantis physiology provides insight into the role of fucosylated HMOs in influencing host- and microbe-microbe interactions within the infant gut microbiome.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Kajal Rawat ◽  
Neha Singh ◽  
Puja Kumari ◽  
Lekha Saha

AbstractThe gut microbiota plays an important role in neurological diseases via the gut–brain axis. Many factors such as diet, antibiotic therapy, stress, metabolism, age, geography and genetics are known to play a critical role in regulating the colonization pattern of the microbiota. Recent studies have shown the role of the low carbohydrate, adequate protein, and high fat “ketogenic diet” in remodeling the composition of the gut microbiome and thereby facilitating protective effects in various central nervous system (CNS) disorders. Gut microbes are found to be involved in the pathogenesis of various CNS disorders like epilepsy, Parkinson’s disease (PD), Alzheimer’s disease (AD), autism spectrum disorders (ASDs), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and stress, anxiety and depression. In vivo studies have shown an intricate link between gut microbes and KD and specific microbes/probiotics proved useful in in vivo CNS disease models. In the present review, we discuss the gut–brain bidirectional axis and the underlying mechanism of KD-based therapy targeting gut microbiome in in vivo animal models and clinical studies in neurological diseases. Also, we tried to infer how KD by altering the microbiota composition contributes towards the protective role in various CNS disorders. This review helps to uncover the mechanisms that are utilized by the KD and gut microbiota to modulate gut–brain axis functions and may provide novel opportunities to target therapies to the gut to treat neurologic disorders.


2020 ◽  
Vol 21 (20) ◽  
pp. 7551
Author(s):  
Kanmani Suganya ◽  
Byung-Soo Koo

The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has the largest and vulnerable surface with desirable features to observe foods, nutrients, and environmental factors, as well as to differentiate commensals, invading pathogens, and others. It is well-known that the gut has a strong connection with the central nervous system (CNS) in the context of health and disease. A healthy gut with diverse microbes is vital for normal brain functions and emotional behaviors. In addition, the CNS controls most aspects of the GI physiology. The molecular interaction between the gut/microbiome and CNS is complex and bidirectional, ensuring the maintenance of gut homeostasis and proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, and metabolites-dependent pathways. Changes in the bidirectional relationship between the GIT and CNS are linked with the pathogenesis of gastrointestinal and neurological disorders; therefore, the microbiota/gut-and-brain axis is an emerging and widely accepted concept. In this review, we summarize the recent findings supporting the role of the gut microbiota and immune system on the maintenance of brain functions and the development of neurological disorders. In addition, we highlight the recent advances in improving of neurological diseases by probiotics/prebiotics/synbiotics and fecal microbiota transplantation via the concept of the gut–brain axis.


2020 ◽  
Vol 19 (7) ◽  
pp. 509-526
Author(s):  
Qin Huang ◽  
Fang Yu ◽  
Di Liao ◽  
Jian Xia

: Recent studies implicate microbiota-brain communication as an essential factor for physiology and pathophysiology in brain function and neurodevelopment. One of the pivotal mechanisms about gut to brain communication is through the regulation and interaction of gut microbiota on the host immune system. In this review, we will discuss the role of microbiota-immune systeminteractions in human neurological disorders. The characteristic features in the development of neurological diseases include gut dysbiosis, the disturbed intestinal/Blood-Brain Barrier (BBB) permeability, the activated inflammatory response, and the changed microbial metabolites. Neurological disorders contribute to gut dysbiosis and some relevant metabolites in a top-down way. In turn, the activated immune system induced by the change of gut microbiota may deteriorate the development of neurological diseases through the disturbed gut/BBB barrier in a down-top way. Understanding the characterization and identification of microbiome-immune- brain signaling pathways will help us to yield novel therapeutic strategies by targeting the gut microbiome in neurological disease.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Guojun Wu ◽  
Naisi Zhao ◽  
Chenhong Zhang ◽  
Yan Y. Lam ◽  
Liping Zhao

AbstractTo demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem’s higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same “guild” if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of “guild” to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases.


Author(s):  
Yue Zhao ◽  
Yuxia Liu ◽  
Shuang Li ◽  
Zhaoyun Peng ◽  
Xiantao Liu ◽  
...  

Abstract Background Lung cancer is the leading cause of cancer-related deaths worldwide (Ferlay et al., Int J Cancer 136:E359–386, 2015). In addition, lung cancer is associated with the highest mortality among all cancer types (Wu et al., Exp Ther Med 16:3004–3010, 2018). Previous studies report that microbiota play an important role in lung cancer. Notably, changes in lung and gut microbiota, are associated with progression of lung cancer. Several studies report that lung and gut microbiome promote lung cancer initiation and development by modulating metabolic pathways, inhibiting the function of immune cells, and producing pro-inflammatory factors. In addition, some factors such as microbiota dysbiosis, affect production of bacteriotoxins, genotoxicity and virulence effect, therefore, they play a key role in cancer progression. These findings imply that lung and gut microbiome are potential markers and targets for lung cancer. However, the role of microbiota in development and progression of lung cancer has not been fully explored. Purpose The aim of this study was to systemically review recent research findings on relationship of lung and gut microbiota with lung cancer. In addition, we explored gut–lung axis and potential mechanisms of lung and gut microbiota in modulating lung cancer progression. Conclusion Pulmonary and intestinal flora influence the occurrence, development, treatment and prognosis of lung cancer, and will provide novel strategies for prevention, diagnosis, and treatment of lung cancer.


Sign in / Sign up

Export Citation Format

Share Document