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19 pages, 2942 KiB

Open AccessArticle

Cell-Free Supernatant Derived from a Lactobacillus casei BL23 Culture Modifies the Antiviral and Immunomodulatory Capacity of Mesenchymal Stromal Cells

by Szabolcs Muzsai, Ore-Matan Maryanovsky, Roland Ander, Gábor Koncz, Anett Mázló, Attila Bácsi and Márta Tóth

Biomedicines 2023, 11(6), 1521; https://doi.org/10.3390/biomedicines11061521 - 24 May 2023

Cited by 1 | Viewed by 2651

Abstract

Immune responses are highly complex and intricately regulated processes involving immune and non-immune cells in close direct and indirect contact with each other. These cells are highly sensitive to environmental signals, including factors derived from microbiota. Here, we demonstrate that the human microbiota [...] Read more.

Immune responses are highly complex and intricately regulated processes involving immune and non-immune cells in close direct and indirect contact with each other. These cells are highly sensitive to environmental signals, including factors derived from microbiota. Here, we demonstrate that the human microbiota member Lactobacillus casei (L. casei)-derived cell-free supernatant (CFS) enhances the sensitivity of mesenchymal-stromal-cell-like (MSCI) cells to viral stimuli and induces the development of dendritic cells (DCs) with anti-inflammatory and antiviral properties via pretreated MSCl cells. Our results showed that the production of INFβ and CXCL10 by MSCl cells upon viral stimulation was dependent on the presence of L. casei-derived extracellular vesicles in CFS during pretreatment. Moreover, L. casei CFS and/or poly (I:C)-conditioned MSCI cells altered the differentiation process of freshly isolated monocytes, as well as the developing DCs’ phenotype and functional activities, such as cytokine and chemokine secretion. Taken together, L. casei CFS contains factors which contribute to the pronounced antiviral response of MSCI cells, avoiding the development of inflammation via the induction of differentiation of anti-inflammatory DCs that retain their antiviral properties. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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16 pages, 2678 KiB

Open AccessArticle

Alterations in Gut Microbiota Composition in Patients with COVID-19: A Pilot Study of Whole Hypervariable 16S rRNA Gene Sequencing

by Dorota Mańkowska-Wierzbicka, Joanna Zuraszek, Adrianna Wierzbicka, Marcin Gabryel, Dagmara Mahadea, Alina Baturo, Oliwia Zakerska-Banaszak, Ryszard Slomski, Marzena Skrzypczak-Zielinska and Agnieszka Dobrowolska

Biomedicines 2023, 11(2), 367; https://doi.org/10.3390/biomedicines11020367 - 27 Jan 2023

Cited by 7 | Viewed by 3605

Abstract

It is crucial to consider the importance of the microbiome and the gut–lung axis in the context of SARS-CoV-2 infection. This pilot study examined the fecal microbial composition of patients with COVID-19 following a 3-month recovery. Using for the first time metagenomic analysis [...] Read more.

It is crucial to consider the importance of the microbiome and the gut–lung axis in the context of SARS-CoV-2 infection. This pilot study examined the fecal microbial composition of patients with COVID-19 following a 3-month recovery. Using for the first time metagenomic analysis based on all hypervariable regions (V1-V9) of the 16S rRNA gene, we have identified 561 microbial species; however, 17 were specific only for the COVID-19 group (n = 8). The patients’ cohorts revealed significantly greater alpha diversity of the gut microbiota compared to healthy controls (n = 14). This finding has been demonstrated by operational taxonomic units (OTUs) richness (p < 0.001) and Chao1 index (p < 0.01). The abundance of the phylum Verrucomicrobia was 30 times higher in COVID-19 patients compared to healthy subjects. Accordingly, this disproportion was also noted at other taxonomic levels: in the class Verrucomicrobiae, the family Verrucomicrobiaceae, and the genus Akkermansia. Elevated pathobionts such as Escherichia coli, Bilophila wadsworthia, and Parabacteroides distasonis were found in COVID-19 patients. Considering the gut microbiota’s ability to disturb the immune response, our findings suggest the importance of the enteric microbiota in the course of SARS-CoV-2 infection. This pilot study shows that the composition of the microbial community may not be fully restored in individuals with SARS-CoV-2 following a 3-month recovery. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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11 pages, 2989 KiB

Open AccessCommunication

Toxin-like Peptides from the Bacterial Cultures Derived from Gut Microbiome Infected by SARS-CoV-2—New Data for a Possible Role in the Long COVID Pattern

by Carlo Brogna, Simone Cristoni, Barbara Brogna, Domenico Rocco Bisaccia, Giuliano Marino, Valentina Viduto, Luigi Montano and Marina Piscopo

Biomedicines 2023, 11(1), 87; https://doi.org/10.3390/biomedicines11010087 - 29 Dec 2022

Cited by 14 | Viewed by 5557

Abstract

It has been 3 years since the beginning of the SARS-CoV-2 outbreak, however it is as yet little known how to care for the acute COVID-19 and long COVID patients. COVID-19 clinical manifestations are of both pulmonary and extra-pulmonary types. Extra-pulmonary ones include [...] Read more.

It has been 3 years since the beginning of the SARS-CoV-2 outbreak, however it is as yet little known how to care for the acute COVID-19 and long COVID patients. COVID-19 clinical manifestations are of both pulmonary and extra-pulmonary types. Extra-pulmonary ones include extreme tiredness (fatigue), shortness of breath, muscle aches, hyposmia, dysgeusia, and other neurological manifestations. In other autoimmune diseases, such as Parkinson’s disease (PD) or Alzheimer’s Disease (AD), it is well known that role of acetylcholine is crucial in olfactory dysfunction. We have already observed the presence of toxin-like peptides in plasma, urine, and faecal samples from COVID-19 patients, which are very similar to molecules known to alter acetylcholine signaling. After observing the production of these peptides in bacterial cultures, we have performed additional proteomics analyses to better understand their behavior and reported the extended data from our latest in vitro experiment. It seems that the gut microbiome continues to produce toxin-like peptides also after the decrease of RNA SARS-CoV-2 viral load at molecular tests. These toxicological interactions between the gut/human microbiome bacteria and the virus suggest a new scenario in the study of the clinical symptoms in long COVID and also in acute COVID-19 patients. It is discussed that in the bacteriophage similar behavior, the presence of toxins produced by bacteria continuously after viral aggression can be blocked using an appropriate combination of certain drugs. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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12 pages, 641 KiB

Open AccessArticle

The Relationship between the Oral Microbiota and Metabolic Syndrome

by Yvonne Prince, Glenda M. Davison, Saarah F. G. Davids, Rajiv T. Erasmus, Andre P. Kengne, Lisa M. Graham, Shanel Raghubeer and Tandi E. Matsha

Biomedicines 2023, 11(1), 3; https://doi.org/10.3390/biomedicines11010003 - 20 Dec 2022

Cited by 1 | Viewed by 2328

Abstract

The oral microbiota plays a crucial role in both systemic inflammation and metabolic syndrome (MetS), which is characterised by low-grade inflammation. Studies have analysed the gut microbiota using stool specimens from subjects with MetS; however, the etiological role of the oral microbiota in [...] Read more.

The oral microbiota plays a crucial role in both systemic inflammation and metabolic syndrome (MetS), which is characterised by low-grade inflammation. Studies have analysed the gut microbiota using stool specimens from subjects with MetS; however, the etiological role of the oral microbiota in the development of MetS is still uncertain. We investigated the oral microbiota of 128 subgingival plaque samples from a South African cohort with and without MetS. After a comprehensive analysis of the oral microbiota, we observed a significant increase in Gram-positive aerobic and anaerobic microbiota in those with MetS. We observed an abundance of Actinomyces, Corynebacterium, and Fusobacterium genera in the MetS group, which differed significantly from previous studies, which found Granulicatella to be enriched in MetS. To further assess the impact of the metabolic parameters (FBG, Waist C, HDL, TGs, and BP) on the oral microbiota, we calculated the odds ratio (ORs) for significant oral microbiota identified between the MetS groups. We found that different species were associated with at least four MetS risk factors. This study has shown that the oral microbiota is disrupted in MetS and may promote inflammation providing a gateway to other systemic diseases, including diabetes and cardiovascular diseases. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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Review

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19 pages, 763 KiB

Open AccessReview

Exploring the Therapeutic Potential of Gamma-Aminobutyric Acid in Stress and Depressive Disorders through the Gut–Brain Axis

by Timur Liwinski, Undine E. Lang, Annette B. Brühl and Else Schneider

Biomedicines 2023, 11(12), 3128; https://doi.org/10.3390/biomedicines11123128 - 24 Nov 2023

Viewed by 1936

Abstract

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABA_A receptors) responsible for [...] Read more.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABA_A receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. GABA is readily available and approved as a food supplement in many countries. Although there is substantial evidence indicating that orally ingested GABA may affect GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that oral GABA intake may exert beneficial effects on the brain and psyche through the gut–brain axis. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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23 pages, 1034 KiB

Open AccessReview

Gut–Kidney–Heart: A Novel Trilogy

by Mario Caldarelli, Laura Franza, Pierluigi Rio, Antonio Gasbarrini, Giovanni Gambassi and Rossella Cianci

Biomedicines 2023, 11(11), 3063; https://doi.org/10.3390/biomedicines11113063 - 15 Nov 2023

Cited by 2 | Viewed by 984

Abstract

The microbiota represents a key factor in determining health and disease. Its role in inflammation and immunological disorders is well known, but it is also involved in several complex conditions, ranging from neurological to psychiatric, from gastrointestinal to cardiovascular diseases. It has recently [...] Read more.

The microbiota represents a key factor in determining health and disease. Its role in inflammation and immunological disorders is well known, but it is also involved in several complex conditions, ranging from neurological to psychiatric, from gastrointestinal to cardiovascular diseases. It has recently been hypothesized that the gut microbiota may act as an intermediary in the close interaction between kidneys and the cardiovascular system, leading to the conceptualization of the “gut–kidney–heart” axis. In this narrative review, we will discuss the impact of the gut microbiota on each system while also reviewing the available data regarding the axis itself. We will also describe the role of gut metabolites in this complex interplay, as well as potential therapeutical perspectives. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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29 pages, 2015 KiB

Open AccessReview

An Overview of Chronic Kidney Disease Pathophysiology: The Impact of Gut Dysbiosis and Oral Disease

by Serena Altamura, Davide Pietropaoli, Francesca Lombardi, Rita Del Pinto and Claudio Ferri

Biomedicines 2023, 11(11), 3033; https://doi.org/10.3390/biomedicines11113033 - 12 Nov 2023

Cited by 2 | Viewed by 2781

Abstract

Chronic kidney disease (CKD) is a severe condition and a significant public health issue worldwide, carrying the burden of an increased risk of cardiovascular events and mortality. The traditional factors that promote the onset and progression of CKD are cardiometabolic risk factors like [...] Read more.

Chronic kidney disease (CKD) is a severe condition and a significant public health issue worldwide, carrying the burden of an increased risk of cardiovascular events and mortality. The traditional factors that promote the onset and progression of CKD are cardiometabolic risk factors like hypertension and diabetes, but non-traditional contributors are escalating. Moreover, gut dysbiosis, inflammation, and an impaired immune response are emerging as crucial mechanisms in the disease pathology. The gut microbiome and kidney disease exert a reciprocal influence commonly referred to as “the gut-kidney axis” through the induction of metabolic, immunological, and endocrine alterations. Periodontal diseases are strictly involved in the gut-kidney axis for their impact on the gut microbiota composition and for the metabolic and immunological alterations occurring in and reciprocally affecting both conditions. This review aims to provide an overview of the dynamic biological interconnections between oral health status, gut, and renal pathophysiology, spotlighting the dynamic oral-gut-kidney axis and raising whether periodontal diseases and gut microbiota can be disease modifiers in CKD. By doing so, we try to offer new insights into therapeutic strategies that may enhance the clinical trajectory of CKD patients, ultimately advancing our quest for improved patient outcomes and well-being. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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12 pages, 1041 KiB

Open AccessReview

Gut Microbiota Alteration and Its Modulation with Probiotics in Celiac Disease

by Angela Saviano, Carmine Petruzziello, Mattia Brigida, Maria Rita Morabito Loprete, Gabriele Savioli, Alessio Migneco and Veronica Ojetti

Biomedicines 2023, 11(10), 2638; https://doi.org/10.3390/biomedicines11102638 - 26 Sep 2023

Cited by 2 | Viewed by 1518

Abstract

Celiac disease (CD) is a chronic inflammation of the small intestine triggered by gluten ingestion in genetically predisposed people. Recent literature studies highlight the possible role of the gut microbiota in the pathogenesis of this disease. The gut microbiota is a complex community [...] Read more.

Celiac disease (CD) is a chronic inflammation of the small intestine triggered by gluten ingestion in genetically predisposed people. Recent literature studies highlight the possible role of the gut microbiota in the pathogenesis of this disease. The gut microbiota is a complex community of microorganisms that can interact with the innate and adaptative immune systems. A condition of dysbiosis, which refers to an alteration in the composition and function of the human gut microbiota, can lead to a dysregulated immune response. This condition may contribute to triggering gluten intolerance, favoring the development and/or progression of CD in genetically susceptible patients. Interestingly, studies on children and adults with CD showed a different microbiome profile in fecal samples, with a different degree of “activity” for the disease. From this point of view, our review aimed to collect and discuss modern evidence about the alteration of the gut microbiota and its modulation with probiotics, with possible future indications in the management of patients affected by CD. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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12 pages, 901 KiB

Open AccessReview

Gut Microbiota, LADA, and Type 1 Diabetes Mellitus: An Evolving Relationship

by Andrea Piccioni, Federico Rosa, Sergio Mannucci, Federica Manca, Giuseppe Merra, Sabrina Chiloiro, Marcello Candelli, Marcello Covino, Antonio Gasbarrini and Francesco Franceschi

Biomedicines 2023, 11(3), 707; https://doi.org/10.3390/biomedicines11030707 - 25 Feb 2023

Cited by 3 | Viewed by 2087

Abstract

There is much evidence confirming the crucial role played by the gut microbiota in modulating the immune system in the onset of autoimmune diseases. In this article, we focus on the relationship between alterations in the microbiome and the onset of diabetes mellitus [...] Read more.

There is much evidence confirming the crucial role played by the gut microbiota in modulating the immune system in the onset of autoimmune diseases. In this article, we focus on the relationship between alterations in the microbiome and the onset of diabetes mellitus type 1 and LADA, in light of the latest evidence. We will then look at both how the role of the gut microbiota appears to be increasingly crucial in the pathogenesis of these disorders and how this aspect may be instrumental in the development of new potential therapeutic strategies that modulate the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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41 pages, 1855 KiB

Open AccessReview

Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy

by Connor Campbell, Mrunmayee R. Kandalgaonkar, Rachel M. Golonka, Beng San Yeoh, Matam Vijay-Kumar and Piu Saha

Biomedicines 2023, 11(2), 294; https://doi.org/10.3390/biomedicines11020294 - 20 Jan 2023

Cited by 31 | Viewed by 9782

Abstract

Gut microbes and their metabolites are actively involved in the development and regulation of host immunity, which can influence disease susceptibility. Herein, we review the most recent research advancements in the gut microbiota–immune axis. We discuss in detail how the gut microbiota is [...] Read more.

Gut microbes and their metabolites are actively involved in the development and regulation of host immunity, which can influence disease susceptibility. Herein, we review the most recent research advancements in the gut microbiota–immune axis. We discuss in detail how the gut microbiota is a tipping point for neonatal immune development as indicated by newly uncovered phenomenon, such as maternal imprinting, in utero intestinal metabolome, and weaning reaction. We describe how the gut microbiota shapes both innate and adaptive immunity with emphasis on the metabolites short-chain fatty acids and secondary bile acids. We also comprehensively delineate how disruption in the microbiota–immune axis results in immune-mediated diseases, such as gastrointestinal infections, inflammatory bowel diseases, cardiometabolic disorders (e.g., cardiovascular diseases, diabetes, and hypertension), autoimmunity (e.g., rheumatoid arthritis), hypersensitivity (e.g., asthma and allergies), psychological disorders (e.g., anxiety), and cancer (e.g., colorectal and hepatic). We further encompass the role of fecal microbiota transplantation, probiotics, prebiotics, and dietary polyphenols in reshaping the gut microbiota and their therapeutic potential. Continuing, we examine how the gut microbiota modulates immune therapies, including immune checkpoint inhibitors, JAK inhibitors, and anti-TNF therapies. We lastly mention the current challenges in metagenomics, germ-free models, and microbiota recapitulation to a achieve fundamental understanding for how gut microbiota regulates immunity. Altogether, this review proposes improving immunotherapy efficacy from the perspective of microbiome-targeted interventions. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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18 pages, 681 KiB

Open AccessReview

The Role of Gut Microbiota in Heart Failure: When Friends Become Enemies

by Rossella Cianci, Laura Franza, Raffaele Borriello, Danilo Pagliari, Antonio Gasbarrini and Giovanni Gambassi

Biomedicines 2022, 10(11), 2712; https://doi.org/10.3390/biomedicines10112712 - 26 Oct 2022

Cited by 9 | Viewed by 2227

Abstract

Heart failure is a complex health issue, with important consequences on the overall wellbeing of patients. It can occur both in acute and chronic forms and, in the latter, the immune system appears to play an important role in the pathogenesis of the [...] Read more.

Heart failure is a complex health issue, with important consequences on the overall wellbeing of patients. It can occur both in acute and chronic forms and, in the latter, the immune system appears to play an important role in the pathogenesis of the disease. In particular, in the forms with preserved ejection fraction or with only mildly reduced ejection fraction, some specific associations with chronic inflammatory diseases have been observed. Another interesting aspect that is worth considering is the role of microbiota modulation, in this context: given the importance of microbiota in the modulation of immune responses, it is possible that changes in its composition may somewhat influence the progression and even the pathogenesis of heart failure. In this narrative review, we aim to examine the relationship between immunity and heart failure, with a special focus on the role of microbiota in this pathological condition. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases)

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