2023

Jump to: 2022, 2021

26 pages, 3795 KiB

Open AccessReview

Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis

by Juanjuan Wang, Ningning Zhu, Xiaomin Su, Yunhuan Gao and Rongcun Yang

Cells 2023, 12(5), 793; https://doi.org/10.3390/cells12050793 - 02 Mar 2023

Cited by 31 | Viewed by 4887

The gut microbiota, including bacteria, archaea, fungi, viruses and phages, inhabits the gastrointestinal tract. This commensal microbiota can contribute to the regulation of host immune response and homeostasis. Alterations of the gut microbiota have been found in many immune-related diseases. The metabolites generated [...] Read more.

The gut microbiota, including bacteria, archaea, fungi, viruses and phages, inhabits the gastrointestinal tract. This commensal microbiota can contribute to the regulation of host immune response and homeostasis. Alterations of the gut microbiota have been found in many immune-related diseases. The metabolites generated by specific microorganisms in the gut microbiota, such as short-chain fatty acids (SCFAs), tryptophan (Trp) and bile acid (BA) metabolites, not only affect genetic and epigenetic regulation but also impact metabolism in the immune cells, including immunosuppressive and inflammatory cells. The immunosuppressive cells (such as tolerogenic macrophages (tMacs), tolerogenic dendritic cells (tDCs), myeloid-derived suppressive cells (MDSCs), regulatory T cells (Tregs), regulatory B cells (Breg) and innate lymphocytes (ILCs)) and inflammatory cells (such as inflammatory Macs (iMacs), DCs, CD4 T helper (Th)1, CD4Th2, Th17, natural killer (NK) T cells, NK cells and neutrophils) can express different receptors for SCFAs, Trp and BA metabolites from different microorganisms. Activation of these receptors not only promotes the differentiation and function of immunosuppressive cells but also inhibits inflammatory cells, causing the reprogramming of the local and systemic immune system to maintain the homeostasis of the individuals. We here will summarize the recent advances in understanding the metabolism of SCFAs, Trp and BA in the gut microbiota and the effects of SCFAs, Trp and BA metabolites on gut and systemic immune homeostasis, especially on the differentiation and functions of the immune cells. Full article

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24 pages, 2431 KiB

Open AccessReview

The Crosstalk between Microbiome and Mitochondrial Homeostasis in Neurodegeneration

by Fivos Borbolis, Eirini Mytilinaiou and Konstantinos Palikaras

Cells 2023, 12(3), 429; https://doi.org/10.3390/cells12030429 - 28 Jan 2023

Cited by 5 | Viewed by 4264

Abstract

Mitochondria are highly dynamic organelles that serve as the primary cellular energy-generating system. Apart from ATP production, they are essential for many biological processes, including calcium homeostasis, lipid biogenesis, ROS regulation and programmed cell death, which collectively render them invaluable for neuronal integrity [...] Read more.

Mitochondria are highly dynamic organelles that serve as the primary cellular energy-generating system. Apart from ATP production, they are essential for many biological processes, including calcium homeostasis, lipid biogenesis, ROS regulation and programmed cell death, which collectively render them invaluable for neuronal integrity and function. Emerging evidence indicates that mitochondrial dysfunction and altered mitochondrial dynamics are crucial hallmarks of a wide variety of neurodevelopmental and neurodegenerative conditions. At the same time, the gut microbiome has been implicated in the pathogenesis of several neurodegenerative disorders due to the bidirectional communication between the gut and the central nervous system, known as the gut–brain axis. Here we summarize new insights into the complex interplay between mitochondria, gut microbiota and neurodegeneration, and we refer to animal models that could elucidate the underlying mechanisms, as well as novel interventions to tackle age-related neurodegenerative conditions, based on this intricate network. Full article

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2022

Jump to: 2023, 2021

25 pages, 8282 KiB

Open AccessArticle

Hyaluronan Regulates Neuronal and Immune Function in the Rat Small Intestine and Colonic Microbiota after Ischemic/Reperfusion Injury

by Annalisa Bosi, Davide Banfi, Michela Bistoletti, Lucia Martina Catizzone, Anna Maria Chiaravalli, Paola Moretto, Elisabetta Moro, Evgenia Karousou, Manuela Viola, Maria Cecilia Giron, Francesca Crema, Carlo Rossetti, Giorgio Binelli, Alberto Passi, Davide Vigetti, Cristina Giaroni and Andreina Baj

Cells 2022, 11(21), 3370; https://doi.org/10.3390/cells11213370 - 25 Oct 2022

Cited by 4 | Viewed by 2141

Abstract

Background: Intestinal ischemia and reperfusion (IRI) injury induces acute and long-lasting damage to the neuromuscular compartment and dysmotility. This study aims to evaluate the pathogenetic role of hyaluronan (HA), a glycosaminoglycan component of the extracellular matrix, as a modulator of the enteric neuronal [...] Read more.

Background: Intestinal ischemia and reperfusion (IRI) injury induces acute and long-lasting damage to the neuromuscular compartment and dysmotility. This study aims to evaluate the pathogenetic role of hyaluronan (HA), a glycosaminoglycan component of the extracellular matrix, as a modulator of the enteric neuronal and immune function and of the colonic microbiota during in vivo IRI in the rat small intestine. Methods: mesenteric ischemia was induced in anesthetized adult male rats for 60 min, followed by 24 h reperfusion. Injured, sham-operated and non-injured animals were treated with the HA synthesis inhibitor, 4-methylumbelliferone (4-MU 25 mg/kg). Fecal microbiota composition was evaluated by Next Generation Sequencing. Neutrophil infiltration, HA homeostasis and toll like receptor (TLR2 and TLR4) expression in the small intestine were evaluated by immunohistochemical and biomolecular approaches (qRT-PCR and Western blotting). Neuromuscular responses were studied in vitro, in the absence and presence of the selective TLR2/4 inhibitor, Sparstolonin B (SsnB 10, 30 µM). Results: 4-MU significantly reduced IRI-induced enhancement of potentially harmful Escherichia and Enterococcus bacteria. After IRI, HA levels, neutrophil infiltration, and TLR2 and TLR4 expression were significantly enhanced in the muscularis propria, and were significantly reduced to baseline levels by 4-MU. In the injured, but not in the non-injured and sham-operated groups, SsnB reduced both electrical field-stimulated (EFS, 0.1–40 Hz) contractions and EFS-induced (10 Hz) non-cholinergic non-adrenergic relaxations. Conclusions: enhanced HA levels after intestinal IRI favors harmful bacteria overgrowth, increases neutrophil infiltration and promotes the upregulation of bacterial target receptors, TLR2 and TLR4, in the muscularis propria, inducing a pro-inflammatory state. TLR2 and TLR4 activation may, however, underlay a provisional benefit on excitatory and inhibitory neuronal pathways underlying peristalsis. Full article

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24 pages, 24409 KiB

Open AccessArticle

Bidirectional Microbiome-Gut-Brain-Axis Communication Influences Metabolic Switch-Associated Responses in the Mosquito Anopheles culicifacies

by Tanwee Das De, Punita Sharma, Sanjay Tevatiya, Charu Chauhan, Seena Kumari, Pooja Yadav, Deepak Singla, Vartika Srivastava, Jyoti Rani, Yasha Hasija, Kailash C. Pandey, Mayur Kajla and Rajnikant Dixit

Cells 2022, 11(11), 1798; https://doi.org/10.3390/cells11111798 - 31 May 2022

Cited by 5 | Viewed by 4163

Abstract

The periodic ingestion of a protein-rich blood meal by adult female mosquitoes causes a drastic metabolic change in their innate physiological status, which is referred to as a ‘metabolic switch’. While understanding the neural circuits for host-seeking is modestly attended, how the gut [...] Read more.

The periodic ingestion of a protein-rich blood meal by adult female mosquitoes causes a drastic metabolic change in their innate physiological status, which is referred to as a ‘metabolic switch’. While understanding the neural circuits for host-seeking is modestly attended, how the gut ‘metabolic switch’ modulates brain functions, and resilience to physiological homeostasis, remains unexplored. Here, through a comparative brain RNA-Seq study, we demonstrate that the protein-rich diet induces the expression of brain transcripts related to mitochondrial function and energy metabolism, possibly causing a shift in the brain’s engagement to manage organismal homeostasis. A dynamic mRNA expression pattern of neuro-signaling and neuro-modulatory genes in both the gut and brain likely establishes an active gut–brain communication. The disruption of this communication through decapitation does not affect the modulation of the neuro-modulator receptor genes in the gut. In parallel, an unusual and paramount shift in the level of neurotransmitters (NTs), from the brain to the gut after blood feeding, further supports the idea of the gut’s ability to serve as a ‘second brain’. After blood-feeding, a moderate enrichment of the gut microbial population, and altered immunity in the gut of histamine receptor-silenced mosquitoes, provide initial evidence that the gut-microbiome plays a crucial role in gut–brain–axis communication. Finally, a comparative metagenomics evaluation of the gut microbiome highlighted that blood-feeding enriches the family members of the Morganellaceae and Pseudomonadaceae bacterial communities. The notable observation of a rapid proliferation of Pseudomonas bacterial sp. and tryptophan enrichment in the gut correlates with the suppression of appetite after blood-feeding. Additionally, altered NTs dynamics of naïve and aseptic mosquitoes provide further evidence that gut-endosymbionts are key modulators for the synthesis of major neuroactive molecules. Our data establish a new conceptual understanding of microbiome–gut–brain–axis communication in mosquitoes. Full article

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18 pages, 736 KiB

Open AccessReview

Microbiota and Pain: Save Your Gut Feeling

by Chiara Morreale, Ilia Bresesti, Annalisa Bosi, Andreina Baj, Cristina Giaroni, Massimo Agosti and Silvia Salvatore

Cells 2022, 11(6), 971; https://doi.org/10.3390/cells11060971 - 11 Mar 2022

Cited by 14 | Viewed by 4840

Abstract

Recently, a growing body of evidence has emerged regarding the interplay between microbiota and the nervous system. This relationship has been associated with several pathological conditions and also with the onset and regulation of pain. Dysregulation of the axis leads to a huge [...] Read more.

Recently, a growing body of evidence has emerged regarding the interplay between microbiota and the nervous system. This relationship has been associated with several pathological conditions and also with the onset and regulation of pain. Dysregulation of the axis leads to a huge variety of diseases such as visceral hypersensitivity, stress-induced hyperalgesia, allodynia, inflammatory pain and functional disorders. In pain management, probiotics have shown promising results. This narrative review describes the peripheral and central mechanisms underlying pain processing and regulation, highlighting the role of the gut-brain axis in the modulation of pain. We summarized the main findings in regard to the stress impact on microbiota’s composition and its influence on pain perception. We also focused on the relationship between gut microbiota and both visceral and inflammatory pain and we provided a summary of the main evidence regarding the mechanistic effects and probiotics use. Full article

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18 pages, 1254 KiB

Open AccessReview

The Microbiota-Gut Axis in Premature Infants: Physio-Pathological Implications

by Ilia Bresesti, Silvia Salvatore, Giorgia Valetti, Andreina Baj, Cristina Giaroni and Massimo Agosti

Cells 2022, 11(3), 379; https://doi.org/10.3390/cells11030379 - 23 Jan 2022

Cited by 18 | Viewed by 4643

Abstract

Intriguing evidence is emerging in regard to the influence of gut microbiota composition and function on host health from the very early stages of life. The development of the saprophytic microflora is conditioned by several factors in infants, and peculiarities have been found [...] Read more.

Intriguing evidence is emerging in regard to the influence of gut microbiota composition and function on host health from the very early stages of life. The development of the saprophytic microflora is conditioned by several factors in infants, and peculiarities have been found for babies born prematurely. This population is particularly exposed to a high risk of infection, postnatal antibiotic treatment, feeding difficulties and neurodevelopmental disabilities. To date, there is still a wide gap in understanding all the determinants and the mechanism behind microbiota disruption and its influence in the development of the most common complications of premature infants. A large body of evidence has emerged during the last decades showing the existence of a bidirectional communication axis involving the gut microbiota, the gut and the brain, defined as the microbiota-gut-brain axis. In this context, given that very few data are available to demonstrate the correlation between microbiota dysbiosis and neurodevelopmental disorders in preterm infants, increasing interest has arisen to better understand the impact of the microbiota-gut-brain axis on the clinical outcomes of premature infants and to clarify how this may lead to alternative preventive, diagnostic and therapeutic strategies. In this review, we explored the current evidence regarding microbiota development in premature infants, focusing on the effects of delivery mode, type of feeding, environmental factors and possible influence of the microbiota-gut-brain axis on preterm clinical outcomes during their hospital stay and on their health status later in life. Full article

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2021

Jump to: 2023, 2022

20 pages, 1470 KiB

Open AccessReview

Hyaluronan: A Neuroimmune Modulator in the Microbiota-Gut Axis

by Annalisa Bosi, Davide Banfi, Michela Bistoletti, Paola Moretto, Elisabetta Moro, Francesca Crema, Fabrizio Maggi, Evgenia Karousou, Manuela Viola, Alberto Passi, Davide Vigetti, Cristina Giaroni and Andreina Baj

Cells 2022, 11(1), 126; https://doi.org/10.3390/cells11010126 - 31 Dec 2021

Cited by 8 | Viewed by 2994

Abstract

The commensal microbiota plays a fundamental role in maintaining host gut homeostasis by controlling several metabolic, neuronal and immune functions. Conversely, changes in the gut microenvironment may alter the saprophytic microbial community and function, hampering the positive relationship with the host. In this [...] Read more.

The commensal microbiota plays a fundamental role in maintaining host gut homeostasis by controlling several metabolic, neuronal and immune functions. Conversely, changes in the gut microenvironment may alter the saprophytic microbial community and function, hampering the positive relationship with the host. In this bidirectional interplay between the gut microbiota and the host, hyaluronan (HA), an unbranched glycosaminoglycan component of the extracellular matrix, has a multifaceted role. HA is fundamental for bacterial metabolism and influences bacterial adhesiveness to the mucosal layer and diffusion across the epithelial barrier. In the host, HA may be produced and distributed in different cellular components within the gut microenvironment, playing a role in the modulation of immune and neuronal responses. This review covers the more recent studies highlighting the relevance of HA as a putative modulator of the communication between luminal bacteria and the host gut neuro-immune axis both in health and disease conditions, such as inflammatory bowel disease and ischemia/reperfusion injury. Full article

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18 pages, 8278 KiB

Open AccessArticle

SCFA Treatment Alleviates Pathological Signs of Migraine and Related Intestinal Alterations in a Mouse Model of NTG-Induced Migraine

by Marika Lanza, Alessia Filippone, Alessio Ardizzone, Giovanna Casili, Irene Paterniti, Emanuela Esposito and Michela Campolo

Cells 2021, 10(10), 2756; https://doi.org/10.3390/cells10102756 - 14 Oct 2021

Cited by 24 | Viewed by 2952

Abstract

Background: There is a growing realization that the gut–brain axis signaling is critical for maintaining the health and homeostasis of the Central Nervous System (CNS) and the intestinal environment. The role of Short-Chain Fatty Acids (SCFAs), such as Sodium Propionate (SP) and Sodium [...] Read more.

Background: There is a growing realization that the gut–brain axis signaling is critical for maintaining the health and homeostasis of the Central Nervous System (CNS) and the intestinal environment. The role of Short-Chain Fatty Acids (SCFAs), such as Sodium Propionate (SP) and Sodium Butyrate (SB), has been reported to counteract inflammation activation in the central and Enteric Nervous System (ENS). Methods: In this study, we evaluated the role of the SCFAs in regulating the pathophysiology of migraine and correlated dysregulations in the gut environment in a mouse model of Nitroglycerine (NTG)-induced migraine. Results: We showed that, following behavioral tests evaluating pain and photophobia, the SP and SB treatments attenuated pain attacks provoked by NTG. Moreover, treatments with both SCFAs reduced histological damage in the trigeminal nerve nucleus and decreased the expression of proinflammatory mediators. Ileum evaluation following NTG injection reported that SCFA treatments importantly restored intestinal mucosa alterations, as well as the release of neurotransmitters in the ENS. Conclusions: Taken together, these results provide evidence that SCFAs exert powerful effects, preventing inflammation through the gut–brain axis, suggesting a new insight into the potential application of SCFAs as novel supportive therapies for migraine and correlated intestinal alterations. Full article

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13 pages, 848 KiB

Open AccessReview

Interplay between Gut Lymphatic Vessels and Microbiota

by Eleonora Solari, Cristiana Marcozzi, Daniela Negrini and Andrea Moriondo

Cells 2021, 10(10), 2584; https://doi.org/10.3390/cells10102584 - 28 Sep 2021

Cited by 8 | Viewed by 6810

Abstract

Lymphatic vessels play a distinctive role in draining fluid, molecules and even cells from interstitial and serosal spaces back to the blood circulation. Lymph vessels of the gut, and especially those located in the villi (called lacteals), not only serve this primary function, [...] Read more.

Lymphatic vessels play a distinctive role in draining fluid, molecules and even cells from interstitial and serosal spaces back to the blood circulation. Lymph vessels of the gut, and especially those located in the villi (called lacteals), not only serve this primary function, but are also responsible for the transport of lipid moieties absorbed by the intestinal mucosa and serve as a second line of defence against possible bacterial infections. Here, we briefly review the current knowledge of the general mechanisms allowing lymph drainage and propulsion and will focus on the most recent findings on the mutual relationship between lacteals and intestinal microbiota. Full article

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29 pages, 6068 KiB

Open AccessArticle

Sex-Dependent Effects of Intestinal Microbiome Manipulation in a Mouse Model of Alzheimer’s Disease

by Harpreet Kaur, Suba Nookala, Surjeet Singh, Santhosh Mukundan, Kumi Nagamoto-Combs and Colin Kelly Combs

Cells 2021, 10(9), 2370; https://doi.org/10.3390/cells10092370 - 09 Sep 2021

Cited by 18 | Viewed by 3456

Abstract

Mechanisms linking intestinal bacteria and neurodegenerative diseases such as Alzheimer’s disease (AD) are still unclear. We hypothesized that intestinal dysbiosis might potentiate AD, and manipulating the microbiome to promote intestinal eubiosis and immune homeostasis may improve AD-related brain changes. This study assessed sex [...] Read more.

Mechanisms linking intestinal bacteria and neurodegenerative diseases such as Alzheimer’s disease (AD) are still unclear. We hypothesized that intestinal dysbiosis might potentiate AD, and manipulating the microbiome to promote intestinal eubiosis and immune homeostasis may improve AD-related brain changes. This study assessed sex differences in the effects of oral probiotic, antibiotics, and synbiotic treatments in the App^NL-G-F mouse model of AD. The fecal microbiome demonstrated significant correlations between bacterial genera in App^NL-G-F mice and Aβ plaque load, gliosis, and memory performance. Female and not male App^NL-G-F mice fed probiotic but not synbiotic exhibited a decrease in Aβ plaques, microgliosis, brain TNF-α, and memory improvement compared to no treatment controls. Although antibiotics treatment did not produce these multiple changes in brain cytokines, memory, or gliosis, it did decrease Aβ plaque load and colon cytokines in App^NL-G-F males. The intestinal cytokine milieu and splenocyte phenotype of female but not male App^NL-G-F mice indicated a modest proinflammatory innate response following probiotic treatment compared to controls, with an adaptive response following antibiotics treatment in male App^NL-G-F mice. Overall, these results demonstrate the beneficial effects of probiotic only in App^NL-G-F females, with minimal benefits of antibiotics or synbiotic feeding in male or female mice. Full article

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17 pages, 388 KiB

Open AccessReview

Helicobacter pylori Infection and Extragastric Diseases—A Focus on the Central Nervous System

by Jacek Baj, Alicja Forma, Wojciech Flieger, Izabela Morawska, Adam Michalski, Grzegorz Buszewicz, Elżbieta Sitarz, Piero Portincasa, Gabriella Garruti, Michał Flieger and Grzegorz Teresiński

Cells 2021, 10(9), 2191; https://doi.org/10.3390/cells10092191 - 25 Aug 2021

Cited by 23 | Viewed by 7301

Abstract

Helicobacter pylori (H. pylori) is most known to cause a wide spectrum of gastrointestinal impairments; however, an increasing number of studies indicates that H. pylori infection might be involved in numerous extragastric diseases such as neurological, dermatological, hematologic, ocular, cardiovascular, metabolic, [...] Read more.

Helicobacter pylori (H. pylori) is most known to cause a wide spectrum of gastrointestinal impairments; however, an increasing number of studies indicates that H. pylori infection might be involved in numerous extragastric diseases such as neurological, dermatological, hematologic, ocular, cardiovascular, metabolic, hepatobiliary, or even allergic diseases. In this review, we focused on the nervous system and aimed to summarize the findings regarding H. pylori infection and its involvement in the induction/progression of neurological disorders. Neurological impairments induced by H. pylori infection are primarily due to impairments in the gut–brain axis (GBA) and to an altered gut microbiota facilitated by H. pylori colonization. Currently, regarding a potential relationship between Helicobacter infection and neurological disorders, most of the studies are mainly focused on H. pylori. Full article

17 pages, 763 KiB

Open AccessReview

Microbiota-Gut-Brain Communication in the SARS-CoV-2 Infection

by Luana M. Manosso, Camila O. Arent, Laura A. Borba, Luciane B. Ceretta, João Quevedo and Gislaine Z. Réus

Cells 2021, 10(8), 1993; https://doi.org/10.3390/cells10081993 - 06 Aug 2021

Cited by 17 | Viewed by 6140

Abstract

The coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome 2 (SARS-CoV-2). In addition to pneumonia, individuals affected by the disease have neurological symptoms. Indeed, SARS-CoV-2 has a neuroinvasive capacity. It is known that the infection caused [...] Read more.

The coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome 2 (SARS-CoV-2). In addition to pneumonia, individuals affected by the disease have neurological symptoms. Indeed, SARS-CoV-2 has a neuroinvasive capacity. It is known that the infection caused by SARS-CoV-2 leads to a cytokine storm. An exacerbated inflammatory state can lead to the blood–brain barrier (BBB) damage as well as to intestinal dysbiosis. These changes, in turn, are associated with microglial activation and reactivity of astrocytes that can promote the degeneration of neurons and be associated with the development of psychiatric disorders and neurodegenerative diseases. Studies also have been shown that SARS-CoV-2 alters the composition and functional activity of the gut microbiota. The microbiota-gut-brain axis provides a bidirectional homeostatic communication pathway. Thus, this review focuses on studies that show the relationship between inflammation and the gut microbiota–brain axis in SARS-CoV-2 infection. Full article

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29 pages, 2107 KiB

Open AccessReview

Characterization of Apis mellifera Gastrointestinal Microbiota and Lactic Acid Bacteria for Honeybee Protection—A Review

by Adriana Nowak, Daria Szczuka, Anna Górczyńska, Ilona Motyl and Dorota Kręgiel

Cells 2021, 10(3), 701; https://doi.org/10.3390/cells10030701 - 22 Mar 2021

Cited by 53 | Viewed by 10796

Abstract

Numerous honeybee (Apis mellifera) products, such as honey, propolis, and bee venom, are used in traditional medicine to prevent illness and promote healing. Therefore, this insect has a huge impact on humans’ way of life and the environment. While the population [...] Read more.

Numerous honeybee (Apis mellifera) products, such as honey, propolis, and bee venom, are used in traditional medicine to prevent illness and promote healing. Therefore, this insect has a huge impact on humans’ way of life and the environment. While the population of A. mellifera is large, there is concern that widespread commercialization of beekeeping, combined with environmental pollution and the action of bee pathogens, has caused significant problems for the health of honeybee populations. One of the strategies to preserve the welfare of honeybees is to better understand and protect their natural microbiota. This paper provides a unique overview of the latest research on the features and functioning of A. mellifera. Honeybee microbiome analysis focuses on both the function and numerous factors affecting it. In addition, we present the characteristics of lactic acid bacteria (LAB) as an important part of the gut community and their special beneficial activities for honeybee health. The idea of probiotics for honeybees as a promising tool to improve their health is widely discussed. Knowledge of the natural gut microbiota provides an opportunity to create a broad strategy for honeybee vitality, including the development of modern probiotic preparations to use instead of conventional antibiotics, environmentally friendly biocides, and biological control agents. Full article

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2023

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