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The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders
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The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 24880

Special Issue Editors

Dr. Daniele Lana

E-Mail Website
Guest Editor
Department of Health Sciences, University of Florence, 50139 Florence, Italy
Interests: neuropharmacology; neurodegeneration; neuroinflammation; glia; microbiota; neurodegenerative diseases; hippocampus; behaviour
Special Issues, Collections and Topics in MDPI journals
Dr. Maria Grazia Giovannini

E-Mail Website
Guest Editor
Department of Health Sciences, University of Florence, 50139 Florence, Italy
Interests: neuroinflammation; memory; aging; cholinergic system; Alzheimer’s disease; hippocampus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The gut and its microbiota (MB-gut) is the largest absorption organ and reservoir of bacteria in the human body. The MB-gut is considered a single system whose interactions give rise to responses that affect the functions of the whole body. The central nervous system is in continuous cross-talk with the MB-gut in the so-called MB-gut–brain axis, and many bottom-to-top pathways, activated by MB products, are necessary for the correct development and physiological functions of the brain.

Dysbiosis contributes to many pathological conditions in both the aged and young population. Elucidating how the MB-gut can affect the central nervous system in aging, Alzheimer’s disease, multiple sclerosis and other neurodegenerative pathologies is of the utmost importance. Understanding the interactions between the MB-gut, the enteric system, immune cells, neurons and glia and their implications for host defense, tissue repair and neurodegeneration will be crucial to identifying new actors in the molecular basis of diseases.

In this regard, it is necessary to follow a multidisciplinary approach extended to all the districts and components of the complex MB-gut–brain axis. In particular, the analysis of the MB-gut-driven alterations in the neuron–astrocyte–microglia triad will highlight neurodegenerative mechanisms related to differential recruitment/activation of glial cells, will improve the knowledge of molecules involved in neurons/glia communication and elucidate MB-gut changes that could prevent and/or delay neurodegeneration.

In this regard, investigators are invited to contribute to this Special Issue with original research articles and review articles that can improve the understanding of the role of MB-gut–brain axis alteration in normal brain aging and neurodegenerative disease.

Dr. Daniele Lana
Prof. Dr. Maria Grazia Giovannini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gut microbiota
  • Alzheimer’s disease
  • multiple sclerosis
  • neurodegenerative diseases
  • neurodegeneration
  • neuroinflammation
  • glia-neuron interaction
  • behaviour

Published Papers (7 papers)

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Editorial

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3 pages, 169 KiB  
Editorial
The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders
by Daniele Lana and Maria Grazia Giovannini
Int. J. Mol. Sci. 2023, 24(10), 8460; https://doi.org/10.3390/ijms24108460 - 09 May 2023
Cited by 3 | Viewed by 1176
Abstract
The gut, along with its microbiota (MB-gut), is the largest absorption organ and reservoir of bacteria in the human body [...] Full article
(This article belongs to the Special Issue The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders)

Research

Jump to: Editorial, Review

15 pages, 3446 KiB  
Article
Study on Anti-Constipation Effects of Hemerocallis citrina Baroni through a Novel Strategy of Network Pharmacology Screening
by Yuxuan Liang, Xiaoyi Wei, Rui Ren, Xuebin Zhang, Xiyao Tang, Jinglan Yang, Xiaoqun Wei, Riming Huang, Gary Hardiman, Yuanming Sun and Hong Wang
Int. J. Mol. Sci. 2023, 24(5), 4844; https://doi.org/10.3390/ijms24054844 - 02 Mar 2023
Cited by 2 | Viewed by 1910
Abstract
Daylily (Hemerocallis citrina Baroni) is an edible plant widely distributed worldwide, especially in Asia. It has traditionally been considered a potential anti-constipation vegetable. This study aimed to investigate the anti-constipation effects of daylily from the perspective of gastro-intestinal transit, defecation parameters, short-chain [...] Read more.
Daylily (Hemerocallis citrina Baroni) is an edible plant widely distributed worldwide, especially in Asia. It has traditionally been considered a potential anti-constipation vegetable. This study aimed to investigate the anti-constipation effects of daylily from the perspective of gastro-intestinal transit, defecation parameters, short-chain organic acids, gut microbiome, transcriptomes and network pharmacology. The results show that dried daylily (DHC) intake accelerated the defecation frequency of mice, while it did not significantly alter the levels of short-chain organic acids in the cecum. The 16S rRNA sequencing showed that DHC elevated the abundance of Akkermansia, Bifidobacterium and Flavonifractor, while it reduced the level of pathogens (such as Helicobacter and Vibrio). Furthermore, a transcriptomics analysis revealed 736 differentially expressed genes (DEGs) after DHC treatment, which are mainly enriched in the olfactory transduction pathway. The integration of transcriptomes and network pharmacology revealed seven overlapping targets (Alb, Drd2, Igf2, Pon1, Tshr, Mc2r and Nalcn). A qPCR analysis further showed that DHC reduced the expression of Alb, Pon1 and Cnr1 in the colon of constipated mice. Our findings provide a novel insight into the anti-constipation effects of DHC. Full article
(This article belongs to the Special Issue The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders)
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21 pages, 3047 KiB  
Article
Microbiome and Metabolome Variation as Indicator of Social Stress in Female Prairie Voles
by Daniel A. Nuccio, Marigny C. Normann, Haiming Zhou, Angela J. Grippo and Pallavi Singh
Int. J. Mol. Sci. 2023, 24(2), 1677; https://doi.org/10.3390/ijms24021677 - 14 Jan 2023
Cited by 2 | Viewed by 2315
Abstract
Social isolation is detrimental to the health of social mammals inducing neurochemical and hormonal changes related to depression and anxiety, as well as impairments of cardiovascular and immune functioning. Likewise, perceptions of loneliness are increasingly recognized as detrimental to human psychological well-being, cognitive [...] Read more.
Social isolation is detrimental to the health of social mammals inducing neurochemical and hormonal changes related to depression and anxiety, as well as impairments of cardiovascular and immune functioning. Likewise, perceptions of loneliness are increasingly recognized as detrimental to human psychological well-being, cognitive functioning, and physical health. Few studies, however, have examined the impact of social isolation on the intestinal microbiome and metabolome. To better understand the impact of social isolation on these systems, intestinal microbiota, and the systemic impact via the gut–brain axis, we employed prairie voles. Physiological stress on female prairie voles (n = 22) either with a same-sex sibling (n = 11) or in isolation (n = 11) for four weeks demonstrated behavioral indicators of increased anxiety and depression in isolated voles (p ≤ 0.01). Bacterial DNA from fecal and colon samples, collected at five time points (T0–4), were sequenced for all nine hypervariable regions of the 16S rRNA gene. Microbiome analyses revealed several differences in gut communities of paired and isolated voles with greater differences at T4. Notably, several taxa associated with host health including Anaerostipes and Lactobacillaceae were more prevalent in paired voles, whereas several taxa associated with known pathogens (e.g., Staphylococcaceae and Enterococcus) or disease were elevated in isolated animals. Similarly, metabolome analyses suggested isolated voles, when compared to paired animals, exhibited differences in metabolites associated with diabetes and colitis. These findings further contribute to our understanding of the harmful effects of social isolation, which cause perturbations in the gut microbiome and serum metabolites. Full article
(This article belongs to the Special Issue The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders)
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20 pages, 6782 KiB  
Article
Comparative Metagenomics and Metabolomes Reveals Abnormal Metabolism Activity Is Associated with Gut Microbiota in Alzheimer’s Disease Mice
by Peilin Sun, Hua Zhu, Xue Li, Weixiong Shi, Yaxi Guo, Xiaopeng Du, Ling Zhang, Lei Su and Chuan Qin
Int. J. Mol. Sci. 2022, 23(19), 11560; https://doi.org/10.3390/ijms231911560 - 30 Sep 2022
Cited by 9 | Viewed by 2473
Abstract
A common symptom in Alzheimer’s disease (AD) is cognitive decline, of which the potential pathogenesis remains unclear. In order to understand the mechanism of gut microbiota in AD, it is necessary to clarify the relationship between gut microbiota and metabolites. Behavioral tests, pathological [...] Read more.
A common symptom in Alzheimer’s disease (AD) is cognitive decline, of which the potential pathogenesis remains unclear. In order to understand the mechanism of gut microbiota in AD, it is necessary to clarify the relationship between gut microbiota and metabolites. Behavioral tests, pathological examination, metagenomics, and metabolomics were applied to analyze the difference of gut microbiota and metabolome between APPswe/PS1ΔE9 (PAP) mice with cognitive decline and age-matched controls, and their possible correlations. Our results showed that PAP mice and health mice had different structures of the bacterial communities in the gut. The abundances and diversities of the bacterial communities in health mice were higher than in PAP mice by metagenomics analysis. The abundances of Libanicoccus massiliensis, Paraprevotella clara, and Lactobacillus amylovorus were significantly increased in PAP mice, while the abundances of Turicibacter sanguinis, Dubosiella newyorkensis, and Prevotella oris were greatly reduced. Furthermore, PAP mice possessed peculiar metabolic phenotypes in stool, serum, and hippocampus relative to WT mice, as is demonstrated by alterations in neurotransmitters metabolism, lipid metabolism, aromatic amino acids metabolism, energy metabolism, vitamin digestion and absorption, and bile metabolism. Microbiota–host metabolic correlation analysis suggests that abnormal metabolism in stool, serum, and hippocampus of PAP mice may be modulated by the gut microbiota, especially T. sanguinis, D. newyorkensis, and P. oris. Therefore, abnormal metabolism activity is associated with gut microbiota in Alzheimer’s disease mice. Our results imply that modifying host metabolism through targeting gut microbiota may be a novel and viable strategy for the prevention and treatment of AD in the future. Full article
(This article belongs to the Special Issue The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders)
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20 pages, 3488 KiB  
Article
Continuous Ingestion of Lacticaseibacillus rhamnosus JB-1 during Chronic Stress Ensures Neurometabolic and Behavioural Stability in Rats
by Agata Chudzik, Tymoteusz Słowik, Katarzyna Kochalska, Anna Pankowska, Artur Łazorczyk, Marta Andres-Mach, Radosław Rola, Greg J. Stanisz and Anna Orzyłowska
Int. J. Mol. Sci. 2022, 23(9), 5173; https://doi.org/10.3390/ijms23095173 - 05 May 2022
Cited by 8 | Viewed by 2442
Abstract
The intestinal microbiome composition and dietary supplementation with psychobiotics can result in neurochemical alterations in the brain, which are possible due to the presence of the brain–gut–microbiome axis. In the present study, magnetic resonance spectroscopy (MRS) and behavioural testing were used to evaluate [...] Read more.
The intestinal microbiome composition and dietary supplementation with psychobiotics can result in neurochemical alterations in the brain, which are possible due to the presence of the brain–gut–microbiome axis. In the present study, magnetic resonance spectroscopy (MRS) and behavioural testing were used to evaluate whether treatment with Lacticaseibacillus rhamnosus JB-1 (JB‑1) bacteria alters brain metabolites’ levels and behaviour during continuous exposure to chronic stress. Twenty Wistar rats were subjected to eight weeks of a chronic unpredictable mild stress protocol. Simultaneously, half of them were fed with JB-1 bacteria, and the second half was given a daily placebo. Animals were examined at three-time points: before starting the stress protocol and after five and eight weeks of stress onset. In the elevated plus maze behavioural test the placebo group displayed increased anxiety expressed by almost complete avoidance of exploration, while the JB-1 dietary supplementation mitigated anxiety which resulted in a longer exploration time. Hippocampal MRS measurements demonstrated a significant decrease in glutamine + glutathione concentration in the placebo group compared to the JB-1 bacteria-supplemented group after five weeks of stress. With the progression of stress the decrease of glutamate, glutathione, taurine, and macromolecular concentrations were observed in the placebo group as compared to baseline. The level of brain metabolites in the JB-1-supplemented rats were stable throughout the experiment, with only the taurine level decreasing between weeks five and eight of stress. These data indicated that the JB-1 bacteria diet might stabilize levels of stress-related neurometabolites in rat brain and could prevent the development of anxiety/depressive-like behaviour. Full article
(This article belongs to the Special Issue The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders)
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Review

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28 pages, 1472 KiB  
Review
The Gut–Immune–Brain Axis: An Important Route for Neuropsychiatric Morbidity in Inflammatory Bowel Disease
by Rebecca Katharina Masanetz, Jürgen Winkler, Beate Winner, Claudia Günther and Patrick Süß
Int. J. Mol. Sci. 2022, 23(19), 11111; https://doi.org/10.3390/ijms231911111 - 21 Sep 2022
Cited by 11 | Viewed by 4404
Abstract
Inflammatory bowel disease (IBD) comprises Crohn’s disease (CD) and ulcerative colitis (UC) and is associated with neuropsychiatric symptoms like anxiety and depression. Both conditions strongly worsen IBD disease burden. In the present review, we summarize the current understanding of the pathogenesis of depression [...] Read more.
Inflammatory bowel disease (IBD) comprises Crohn’s disease (CD) and ulcerative colitis (UC) and is associated with neuropsychiatric symptoms like anxiety and depression. Both conditions strongly worsen IBD disease burden. In the present review, we summarize the current understanding of the pathogenesis of depression and anxiety in IBD. We present a stepwise cascade along a gut–immune–brain axis initiated by evasion of chronic intestinal inflammation to pass the epithelial and vascular barrier in the gut and cause systemic inflammation. We then summarize different anatomical transmission routes of gut-derived peripheral inflammation into the central nervous system (CNS) and highlight the current knowledge on neuroinflammatory changes in the CNS of preclinical IBD mouse models with a focus on microglia, the brain-resident macrophages. Subsequently, we discuss how neuroinflammation in IBD can alter neuronal circuitry to trigger symptoms like depression and anxiety. Finally, the role of intestinal microbiota in the gut–immune–brain axis in IBD will be reviewed. A more comprehensive understanding of the interaction between the gastrointestinal tract, the immune system and the CNS accounting for the similarities and differences between UC and CD will pave the path for improved prediction and treatment of neuropsychiatric comorbidities in IBD and other inflammatory diseases. Full article
(This article belongs to the Special Issue The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders)
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16 pages, 1112 KiB  
Review
Drugs, Guts, Brains, but Not Rock and Roll: The Need to Consider the Role of Gut Microbiota in Contemporary Mental Health and Wellness of Emerging Adults
by Ju Eun Lee, David Walton, Colleen P. O’Connor, Michael Wammes, Jeremy P. Burton and Elizabeth A. Osuch
Int. J. Mol. Sci. 2022, 23(12), 6643; https://doi.org/10.3390/ijms23126643 - 14 Jun 2022
Cited by 8 | Viewed by 8816
Abstract
Emerging adulthood (ages 18–25) is a critical period for neurobiological development and the maturation of the hypothalamic–pituitary–adrenal axis. Recent findings also suggest that a natural perturbation of the gut microbiota (GM), combined with other factors, may create a unique vulnerability during this period [...] Read more.
Emerging adulthood (ages 18–25) is a critical period for neurobiological development and the maturation of the hypothalamic–pituitary–adrenal axis. Recent findings also suggest that a natural perturbation of the gut microbiota (GM), combined with other factors, may create a unique vulnerability during this period of life. The GM of emerging adults is thought to be simpler, less diverse, and more unstable than either younger or older people. We postulate that this plasticity in the GM suggests a role in the rising mental health issues seen in westernized societies today via the gut–brain–microbiota axis. Studies have paid particular attention to the diversity of the microbiota, the specific function and abundance of bacteria, and the production of metabolites. In this narrative review, we focus specifically on diet, physical activity/exercise, substance use, and sleep in the context of the emerging adult. We propose that this is a crucial period for establishing a stable and more resilient microbiome for optimal health into adulthood. Recommendations will be made about future research into possible behavioral adjustments that may be beneficial to endorse during this critical period to reduce the probability of a “dysbiotic” GM and the emergence and severity of mental health concerns. Full article
(This article belongs to the Special Issue The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders)
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