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15 pages, 2116 KiB

Open AccessArticle

Illustration of Gut–Thyroid Axis in Alcohol Use Disorder: Interplay of Gut Dysfunction, Pro-Inflammatory Responses, and Thyroid Function

by Manasa Sagaram, Amor J. Royer, Huirong Hu, Abhas Rajhans, Ranganathan Parthasarathy, Sathya Sridevi Krishnasamy, Sri Prakash Mokshagundam, Maiying Kong, Melanie L. Schwandt, Dipendra Parajuli, Matthew C. Cave and Vatsalya Vatsalya

Cells 2022, 11(19), 3100; https://doi.org/10.3390/cells11193100 - 1 Oct 2022

Cited by 4 | Viewed by 2285

Abstract

(1) Background: Heavy and chronic alcohol drinking leads to altered gut dysfunction, coupled with a pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by heavy and chronic alcohol intake; however, the mechanism for altered gut-derived changes in thyroid function has not been [...] Read more.

(1) Background: Heavy and chronic alcohol drinking leads to altered gut dysfunction, coupled with a pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by heavy and chronic alcohol intake; however, the mechanism for altered gut-derived changes in thyroid function has not been studied thus far. This study investigates the role of alcohol-induced gut dysfunction and pro-inflammatory cytokine profile in the thyroid function of patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n = 44) were divided into Gr.1, patients with normal thyroid-stimulating hormone (TSH) levels (n = 28, 0.8 ≤ TSH ≤ 3 mIU/L); and Gr.2, patients with clinically elevated TSH levels (n = 16, TSH > 3 mIU/L). Demographics, drinking measures, comprehensive metabolic panels, and candidate thyroid markers (TSH, circulating triiodothyronine (T3), and free thyroxine (fT4)) were analyzed. Gut-dysfunction-associated markers (lipopolysaccharide (LPS), LPS-binding protein (LBP), and soluble LPS-induced pathogen-associated protein (sCD14)), and candidate pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were also evaluated. (3) Results: Patients in both groups presented with a borderline overweight BMI category. Gr.2 reported numerically higher indices of chronic and heavy drinking patterns than Gr.1. The fT4 levels were elevated, while T3 was within normal limits in both groups. The gut dysfunction markers LBP and sCD14 were numerically elevated in Gr.2 vs. Gr.1, suggesting subtle ongoing changes. Candidate pro-inflammatory cytokines were significantly elevated in Gr.2, including IL-1 β, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect on the gut–immune–thyroid response (r = 0.896, 36 p = 0.002) on TSH levels in a multivariate regression model with LBP, sCD14, and PAI-1 levels as upstream variables in the gut–thyroid pathway. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area = 0.774, 39 p < 0.001) and TNF-α (area = 0.708, p = 0.017), among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4, as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and a lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation by employing the gut–brain axis. These results also emphasize potential directions to carefully evaluate thyroid dysregulation in the overall medical management of AUD. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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19 pages, 1445 KiB

Open AccessArticle

Multi-Strain Probiotic Mixture Affects Brain Morphology and Resting State Brain Function in Healthy Subjects: An RCT

by Julia Rode, Hanna M. T. Edebol Carlman, Julia König, Ashley N. Hutchinson, Per Thunberg, Jonas Persson and Robert J. Brummer

Cells 2022, 11(18), 2922; https://doi.org/10.3390/cells11182922 - 19 Sep 2022

Cited by 18 | Viewed by 7248

Abstract

Probiotics can alter brain function via the gut–brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 [...] Read more.

Probiotics can alter brain function via the gut–brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 years) underwent four-week intervention periods with probiotics and placebo, separated by a four-week washout period. Voxel-based morphometry indicated that the probiotic intervention affected the gray matter volume of a cluster covering the left supramarginal gyrus and superior parietal lobule (p < 0.0001), two regions that were also among those with an altered resting state functional connectivity. Probiotic intervention resulted in significant (FDR < 0.05) functional connectivity changes between regions within the default mode, salience, frontoparietal as well as the language network and several regions located outside these networks. Psychological symptoms trended towards improvement after probiotic intervention, i.e., the total score of the Hospital Anxiety and Depression Scale (p = 0.056) and its depression sub-score (p = 0.093), as well as sleep patterns (p = 0.058). The probiotic intervention evoked distinct changes in brain morphology and resting state brain function alongside slight improvements of psycho(bio)logical markers of the gut–brain axis. The combination of those parameters may provide new insights into the modes of action by which gut microbiota can affect gut–brain communication and hence brain function. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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15 pages, 2191 KiB

Open AccessEditor’s ChoiceArticle

A Multi-Strain Probiotic Formulation Improves Intestinal Barrier Function by the Modulation of Tight and Adherent Junction Proteins

by Raffaella di Vito, Carmela Conte and Giovanna Traina

Cells 2022, 11(16), 2617; https://doi.org/10.3390/cells11162617 - 22 Aug 2022

Cited by 24 | Viewed by 5859

Abstract

In healthy individuals, tight junction proteins (TJPs) maintain the integrity of the intestinal barrier. Dysbiosis and increased intestinal permeability are observed in several diseases, such as inflammatory bowel disease. Many studies highlight the role of probiotics in preventing intestinal barrier dysfunction. The present [...] Read more.

In healthy individuals, tight junction proteins (TJPs) maintain the integrity of the intestinal barrier. Dysbiosis and increased intestinal permeability are observed in several diseases, such as inflammatory bowel disease. Many studies highlight the role of probiotics in preventing intestinal barrier dysfunction. The present study aims to investigate the effects of a commercially available probiotic formulation of L. rhamnosus LR 32, B. lactis BL 04, and B. longum BB 536 (Serobioma, Bromatech s.r.l., Milan, Italy) on TJPs and the integrity of the intestinal epithelial barrier, and the ability of this formulation to prevent lipopolysaccharide-induced, inflammation-associated damage. An in vitro model of the intestinal barrier was developed using a Caco-2 cell monolayer. The mRNA expression levels of the TJ genes were analyzed using real-time PCR. Changes in the amounts of proteins were assessed with Western blotting. The effect of Serobioma on the intestinal epithelial barrier function was assessed using transepithelial electrical resistance (TEER) measurements. The probiotic formulation tested in this study modulates the expression of TJPs and prevents inflammatory damage. Our findings provide new insights into the mechanisms by which probiotics are able to prevent damage to the gut epithelial barrier. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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19 pages, 3208 KiB

Open AccessArticle

Food Reward Alterations during Obesity Are Associated with Inflammation in the Striatum in Mice: Beneficial Effects of Akkermansia muciniphila

by Sabrina J. P. Huwart, Alice de Wouters d’Oplinter, Marialetizia Rastelli, Matthias Van Hul, Willem M. de Vos, Serge Luquet, Patrice D. Cani and Amandine Everard

Cells 2022, 11(16), 2534; https://doi.org/10.3390/cells11162534 - 16 Aug 2022

Cited by 11 | Viewed by 3533

Abstract

The reward system involved in hedonic food intake presents neuronal and behavioral dysregulations during obesity. Moreover, gut microbiota dysbiosis during obesity promotes low-grade inflammation in peripheral organs and in the brain contributing to metabolic alterations. The mechanisms underlying reward dysregulations during obesity remain [...] Read more.

The reward system involved in hedonic food intake presents neuronal and behavioral dysregulations during obesity. Moreover, gut microbiota dysbiosis during obesity promotes low-grade inflammation in peripheral organs and in the brain contributing to metabolic alterations. The mechanisms underlying reward dysregulations during obesity remain unclear. We investigated if inflammation affects the striatum during obesity using a cohort of control-fed or diet-induced obese (DIO) male mice. We tested the potential effects of specific gut bacteria on the reward system during obesity by administrating Akkermansia muciniphila daily or a placebo to DIO male mice. We showed that dysregulations of the food reward are associated with inflammation and alterations in the blood–brain barrier in the striatum of obese mice. We identified Akkermansia muciniphila as a novel actor able to improve the dysregulated reward behaviors associated with obesity, potentially through a decreased activation of inflammatory pathways and lipid-sensing ability in the striatum. These results open a new field of research and suggest that gut microbes can be considered as an innovative therapeutic approach to attenuate reward alterations in obesity. This study provides substance for further investigations of Akkermansia muciniphila-mediated behavioral improvements in other inflammatory neuropsychiatric disorders. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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15 pages, 2713 KiB

Open AccessArticle

Prophylactic Treatment of Undernourished Mice with Cotrimoxazole Induces a Different Profile of Dysbiosis with Functional Metabolic Alterations

by Lívia Budziarek Eslabão, Gabriela Farias Gubert, Lucas Cafferati Beltrame, Isis M. A. Mello, Oscar Bruna-Romero and Carlos R. Zárate-Bladés

Cells 2022, 11(15), 2278; https://doi.org/10.3390/cells11152278 - 23 Jul 2022

Cited by 3 | Viewed by 1854

Abstract

Childhood malnutrition affects physiology and development. It increases infection rates, which may not present clinical signs in severe cases. The World Health Organization recommends prophylactic treatment with cotrimoxazole (SXT) and nutritional recovery to overcome this issue. This treatment is controversial, since evidence of [...] Read more.

Childhood malnutrition affects physiology and development. It increases infection rates, which may not present clinical signs in severe cases. The World Health Organization recommends prophylactic treatment with cotrimoxazole (SXT) and nutritional recovery to overcome this issue. This treatment is controversial, since evidence of a reduction in morbidity and mortality is not a consensus and could induce the development of antibiotic-resistant bacteria. Moreover, the impact of using this wide-spectrum antibiotic on gut microbiota in a critical period of development, and weakness is unknown. To understand how SXT prophylaxis could affect gut microbiota in undernutrition, we induced protein–energy undernutrition (PEU) in weaning C57BL/6 mice for three weeks and treated animals with SXT for two weeks. Using 16S rRNA gene sequencing, we compared the taxonomic composition and metabolic pathways of control mice, animals submitted to undernutrition (UND), treated with SXT, or undernourished and SXT treated (UND + SXT). We identified that UND mice had a significant increase in predicted pathways related to metabolic syndromes later in life. The prophylactic SXT treatment alone resulted in a significant loss in community richness and beta diversity. Furthermore, we identified the reduction of three genera in SXT treated mice, including the butyrate producers Faecalibacterium and Anaerotruncus. Both UND and double challenge (UND + SXT) resulted in a reduction of the amino acid’s biosynthesis pathway related to cell growth. Our results show that the SXT prophylaxis of young mice during an undernourishment period did not re-establish the undernourished microbiota community composition similar to healthy controls but induced a distinct dysbiotic profile with functional metabolic consequences. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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24 pages, 7356 KiB

Open AccessArticle

Identification and Characterization of a Novel Species of Genus Akkermansia with Metabolic Health Effects in a Diet-Induced Obesity Mouse Model

by Ritesh Kumar, Helene Kane, Qiong Wang, Ashley Hibberd, Henrik Max Jensen, Hye-Sook Kim, Steffen Yde Bak, Isabelle Auzanneau, Stéphanie Bry, Niels Christensen, Andrew Friedman, Pia Rasinkangas, Arthur C. Ouwehand, Sofia D. Forssten and Oliver Hasselwander

Cells 2022, 11(13), 2084; https://doi.org/10.3390/cells11132084 - 30 Jun 2022

Cited by 12 | Viewed by 5109

Abstract

Akkermansia muciniphila is a well-known bacterium with the ability to degrade mucin. This metabolic capability is believed to play an important role in the colonization of this bacterium in the gut. In this study, we report the identification and characterization of a novel [...] Read more.

Akkermansia muciniphila is a well-known bacterium with the ability to degrade mucin. This metabolic capability is believed to play an important role in the colonization of this bacterium in the gut. In this study, we report the identification and characterization of a novel Akkermansia sp. DSM 33459 isolated from human feces of a healthy donor. Phylogenetic analysis based on the genome-wide average nucleotide identity indicated that the Akkermansia sp. DSM 33459 has only 87.5% similarity with the type strain A. muciniphila ATCC BAA-835. Akkermansia sp. DSM 33459 showed significant differences in its fatty acid profile and carbon utilization as compared to the type strain. The Akkermansia sp. DSM 33459 strain was tested in a preclinical obesity model to determine its effect on metabolic markers. Akkermansia sp. DSM 33459 showed significant improvement in body weight, total fat weight, and resistin and insulin levels. Interestingly, these effects were more pronounced with the live form as compared to a pasteurized form of the strain. The strain showed production of agmatine, suggesting a potential novel mechanism for supporting metabolic and cognitive health. Based on its phenotypic features and phylogenetic position, it is proposed that this isolate represents a novel species in the genus Akkermansia and a promising therapeutic candidate for the management of metabolic diseases. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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24 pages, 5602 KiB

Open AccessArticle

Effects of Traumatic Brain Injury on the Gut Microbiota Composition and Serum Amino Acid Profile in Rats

by Anastasiia Taraskina, Olga Ignatyeva, Darya Lisovaya, Mikhail Ivanov, Lyudmila Ivanova, Viktoriya Golovicheva, Galina Baydakova, Denis Silachev, Vasiliy Popkov, Tatyana Ivanets, Daria Kashtanova, Vladimir Yudin, Valentin Makarov, Ivan Abramov, Mariya Lukashina, Vera Rakova, Anzhelika Zagainova, Dmitry Zorov, Egor Plotnikov, Gennadiy Sukhikh and Sergey Yudin Show full author list Hide full author list

Cells 2022, 11(9), 1409; https://doi.org/10.3390/cells11091409 - 21 Apr 2022

Cited by 27 | Viewed by 4086

Abstract

Traumatic brain injury (TBI) heavily impacts the body: it damages the brain tissue and the peripheral nervous system and shifts homeostasis in many types of tissue. An acute brain injury compromises the “brain–gut-microbiome axis”, a well-balanced network formed by the brain, gastrointestinal tract, [...] Read more.

Traumatic brain injury (TBI) heavily impacts the body: it damages the brain tissue and the peripheral nervous system and shifts homeostasis in many types of tissue. An acute brain injury compromises the “brain–gut-microbiome axis”, a well-balanced network formed by the brain, gastrointestinal tract, and gut microbiome, which has a complex effect: damage to the brain alters the composition of the microbiome; the altered microbiome affects TBI severity, neuroplasticity, and metabolic pathways through various bacterial metabolites. We modeled TBI in rats. Using a bioinformatics approach, we sought to identify correlations between the gut microbiome composition, TBI severity, the rate of neurological function recovery, and blood metabolome. We found that the TBI caused changes in the abundance of 26 bacterial genera. The most dramatic change was observed in the abundance of Agathobacter species. The TBI also altered concentrations of several metabolites, specifically citrulline and tryptophan. We found no significant correlations between TBI severity and the pre-existing gut microbiota composition or blood metabolites. However, we discovered some differences between the two groups of subjects that showed high and low rates of neurological function recovery, respectively. The present study highlights the role of the brain–gut-microbiome axis in TBI. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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16 pages, 3362 KiB

Open AccessArticle

Intestinal Microbiota Remodeling Protects Mice from Western Diet-Induced Brain Inflammation and Cognitive Decline

by Prasant Kumar Jena, Tahereh Setayesh, Lili Sheng, Jacopo Di Lucente, Lee Way Jin and Yu-Jui Yvonne Wan

Cells 2022, 11(3), 504; https://doi.org/10.3390/cells11030504 - 1 Feb 2022

Cited by 15 | Viewed by 4313

Abstract

It has been shown that the Western diet (WD) induces systemic inflammation and cognitive decline. Moreover, probiotic supplementation and antibiotic treatment reduce diet-induced hepatic inflammation. The current study examines whether shaping the gut microbes by Bifidobacterium infantis (B. infantis) supplementation and [...] Read more.

It has been shown that the Western diet (WD) induces systemic inflammation and cognitive decline. Moreover, probiotic supplementation and antibiotic treatment reduce diet-induced hepatic inflammation. The current study examines whether shaping the gut microbes by Bifidobacterium infantis (B. infantis) supplementation and antibiotic treatment reduce diet-induced brain inflammation and improve neuroplasticity. Furthermore, the significance of bile acid (BA) signaling in regulating brain inflammation was studied. Mice were fed a control diet (CD) or WD for seven months. B. infantis was supplemented to WD-fed mice to study brain inflammation, lipid, metabolomes, and neuroplasticity measured by long-term potentiation (LTP). Broad-spectrum coverage antibiotics and cholestyramine treatments were performed to study the impact of WD-associated gut microbes and BA in brain inflammation. Probiotic B. infantis supplementation inhibited diet-induced brain inflammation by reducing IL6, TNFα, and CD11b levels. B. infantis improved LTP and increased brain PSD95 and BDNF levels, which were reduced due to WD intake. Additionally, B. infantis reduced cecal cholesterol, brain ceramide and enhanced saturated fatty acids. Moreover, antibiotic treatment, as well as cholestyramine, diminished WD-induced brain inflammatory signaling. Our findings support the theory that intestinal microbiota remodeling by B. infantis reduces brain inflammation, activates BA receptor signaling, and improves neuroplasticity. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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18 pages, 11058 KiB

Open AccessArticle

Long-Term Safety Following Faecal Microbiota Transplantation as a Treatment for Recurrent Clostridioides difficile Infection Compared with Patients Treated with a Fixed Bacterial Mixture: Results from a Retrospective Cohort Study

by Frederik Cold, Camilla Kara Svensson, Andreas Munk Petersen, Lars Hestbjerg Hansen and Morten Helms

Cells 2022, 11(3), 435; https://doi.org/10.3390/cells11030435 - 27 Jan 2022

Cited by 12 | Viewed by 5075

Abstract

Faecal microbiota transplantation (FMT) is the recommended treatment for recurrent C. difficile infection (rCDI) following a second recurrence. FMT is considered safe in the short term when procedures for the screening of donors and transferred material are followed. However, the long-term safety profile [...] Read more.

Faecal microbiota transplantation (FMT) is the recommended treatment for recurrent C. difficile infection (rCDI) following a second recurrence. FMT is considered safe in the short term when procedures for the screening of donors and transferred material are followed. However, the long-term safety profile of FMT treatment is largely unknown. In a retrospective cohort study, we assessed the long-term safety of patients treated for rCDI with FMT or a fixed bacterial mixture, rectal bacteriotherapy (RBT). The overall survival, risk of hospital admission, onset of certain pre-specified diseases (cancer, diabetes mellitus, hypertension and inflammatory bowel disease) and risk of being diagnosed with a multidrug-resistant organism were assessed by undertaking a review of the treated patients’ medical records for up to five years following treatment. A total of 280 patients were treated for rCDI with FMT (n = 145) or RBT (n = 135) between 2016 and 2020. In the five years following treatment, there were no differences in survival (adjusted hazard ratio (aHR) 1.03; 95% CI 0.68–1.56), p = 0.89), risk of hospital admission ((aHR 0.92; 95% CI 0.72–1.18), p = 0.5) or onset of any of the analysed diseases. In conclusion, FMT was not associated with increased mortality, risk of hospital admission or onset of disease following treatment when compared with RBT. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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24 pages, 3229 KiB

Open AccessArticle

A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection

by Tanya M. Monaghan, Niharika A. Duggal, Elisa Rosati, Ruth Griffin, Jamie Hughes, Brandi Roach, David Y. Yang, Christopher Wang, Karen Wong, Lynora Saxinger, Maja Pučić-Baković, Frano Vučković, Filip Klicek, Gordan Lauc, Paddy Tighe, Benjamin H. Mullish, Jesus Miguens Blanco, Julie A. K. McDonald, Julian R. Marchesi, Ning Xue, Tania Dottorini, Animesh Acharjee, Andre Franke, Yingrui Li, Gane Ka-Shu Wong, Christos Polytarchou, Tung On Yau, Niki Christodoulou, Maria Hatziapostolou, Minkun Wang, Lindsey A. Russell and Dina H. Kao Show full author list Hide full author list

Cells 2021, 10(11), 3234; https://doi.org/10.3390/cells10113234 - 19 Nov 2021

Cited by 12 | Viewed by 6404

Abstract

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using [...] Read more.

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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Review

Jump to: Research

30 pages, 1914 KiB

Open AccessReview

The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders

by Nikhilesh Anand, Vasavi Rakesh Gorantla and Saravana Babu Chidambaram

Cells 2023, 12(1), 54; https://doi.org/10.3390/cells12010054 - 23 Dec 2022

Cited by 47 | Viewed by 7135

Abstract

Mounting evidence shows that the complex gut microbial ecosystem in the human gastrointestinal (GI) tract regulates the physiology of the central nervous system (CNS) via microbiota and the gut–brain (MGB) axis. The GI microbial ecosystem communicates with the brain through the neuroendocrine, immune, [...] Read more.

Mounting evidence shows that the complex gut microbial ecosystem in the human gastrointestinal (GI) tract regulates the physiology of the central nervous system (CNS) via microbiota and the gut–brain (MGB) axis. The GI microbial ecosystem communicates with the brain through the neuroendocrine, immune, and autonomic nervous systems. Recent studies have bolstered the involvement of dysfunctional MGB axis signaling in the pathophysiology of several neurodegenerative, neurodevelopmental, and neuropsychiatric disorders (NPDs). Several investigations on the dynamic microbial system and genetic–environmental interactions with the gut microbiota (GM) have shown that changes in the composition, diversity and/or functions of gut microbes (termed “gut dysbiosis” (GD)) affect neuropsychiatric health by inducing alterations in the signaling pathways of the MGB axis. Interestingly, both preclinical and clinical evidence shows a positive correlation between GD and the pathogenesis and progression of NPDs. Long-term GD leads to overstimulation of hypothalamic–pituitary–adrenal (HPA) axis and the neuroimmune system, along with altered neurotransmitter levels, resulting in dysfunctional signal transduction, inflammation, increased oxidative stress (OS), mitochondrial dysfunction, and neuronal death. Further studies on the MGB axis have highlighted the significance of GM in the development of brain regions specific to stress-related behaviors, including depression and anxiety, and the immune system in the early life. GD-mediated deregulation of the MGB axis imbalances host homeostasis significantly by disrupting the integrity of the intestinal and blood–brain barrier (BBB), mucus secretion, and gut immune and brain immune functions. This review collates evidence on the potential interaction between GD and NPDs from preclinical and clinical data. Additionally, we summarize the use of non-therapeutic modulators such as pro-, pre-, syn- and post-biotics, and specific diets or fecal microbiota transplantation (FMT), which are promising targets for the management of NPDs. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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24 pages, 1098 KiB

Open AccessReview

Interventions on Gut Microbiota for Healthy Aging

by Sabrina Donati Zeppa, Deborah Agostini, Fabio Ferrini, Marco Gervasi, Elena Barbieri, Alessia Bartolacci, Giovanni Piccoli, Roberta Saltarelli, Piero Sestili and Vilberto Stocchi

Cells 2023, 12(1), 34; https://doi.org/10.3390/cells12010034 - 22 Dec 2022

Cited by 37 | Viewed by 8954

Abstract

In recent years, the improvement in health and social conditions has led to an increase in the average lifespan. Since aging is the most important risk factor for the majority of chronic human diseases, the development of therapies and intervention to stop, lessen [...] Read more.

In recent years, the improvement in health and social conditions has led to an increase in the average lifespan. Since aging is the most important risk factor for the majority of chronic human diseases, the development of therapies and intervention to stop, lessen or even reverse various age-related morbidities is an important target to ameliorate the quality of life of the elderly. The gut microbiota, that is, the complex ecosystem of microorganisms living in the gastrointestinal tract, plays an important role, not yet fully understood, in maintaining the host’s health and homeostasis, influencing metabolic, oxidative and cognitive status; for this reason, it is also named “the forgotten endocrine organ” or “the second brain”. On the other hand, the gut microbiota diversity and richness are affected by unmodifiable factors, such as aging and sex, and modifiable ones, such as diet, pharmacological therapies and lifestyle. In this review, we discuss the changes, mostly disadvantageous, for human health, induced by aging, in microbiota composition and the effects of dietary intervention, of supplementation with probiotics, prebiotics, synbiotics, psychobiotics and antioxidants and of physical exercise. The development of an integrated strategy to implement microbiota health will help in the goal of healthy aging. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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20 pages, 1303 KiB

Open AccessReview

Gut Microbiota in Nutrition and Health with a Special Focus on Specific Bacterial Clusters

by Lucas R. F. Bresser, Marcus C. de Goffau, Evgeni Levin and Max Nieuwdorp

Cells 2022, 11(19), 3091; https://doi.org/10.3390/cells11193091 - 30 Sep 2022

Cited by 16 | Viewed by 5136

Abstract

Health is influenced by how the gut microbiome develops as a result of external and internal factors, such as nutrition, the environment, medication use, age, sex, and genetics. Alpha and beta diversity metrics and (enterotype) clustering methods are commonly employed to perform population [...] Read more.

Health is influenced by how the gut microbiome develops as a result of external and internal factors, such as nutrition, the environment, medication use, age, sex, and genetics. Alpha and beta diversity metrics and (enterotype) clustering methods are commonly employed to perform population studies and to analyse the effects of various treatments, yet, with the continuous development of (new) sequencing technologies, and as various omics fields as a result become more accessible for investigation, increasingly sophisticated methodologies are needed and indeed being developed in order to disentangle the complex ways in which the gut microbiome and health are intertwined. Diseases of affluence, such as type 2 diabetes (T2D) and cardiovascular diseases (CVD), are commonly linked to species associated with the Bacteroides enterotype(s) and a decline of various (beneficial) complex microbial trophic networks, which are in turn linked to the aforementioned factors. In this review, we (1) explore the effects that some of the most common internal and external factors have on the gut microbiome composition and how these in turn relate to T2D and CVD, and (2) discuss research opportunities enabled by and the limitations of some of the latest technical developments in the microbiome sector, including the use of artificial intelligence (AI), strain tracking, and peak to trough ratios. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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17 pages, 1019 KiB

Open AccessReview

Targeting the Gut Microbiome to Treat Metabolic Dysfunction-Associated Fatty Liver Disease: Ready for Prime Time?

by Nicolas Lanthier and Nathalie Delzenne

Cells 2022, 11(17), 2718; https://doi.org/10.3390/cells11172718 - 31 Aug 2022

Cited by 16 | Viewed by 3805

Abstract

Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. Animal studies have also shown a causal role of gut microbiota in liver metabolic disorders including steatosis whereas the human situation is less clear. Patients with metabolic dysfunction [...] Read more.

Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. Animal studies have also shown a causal role of gut microbiota in liver metabolic disorders including steatosis whereas the human situation is less clear. Patients with metabolic dysfunction associated fatty liver disease (MAFLD) also have a modification in their gut microbiota composition but the changes are not fully characterized. The absence of consensus on a precise signature is probably due to disease heterogeneity, possible concomitant medications and different selection or evaluation criteria. The most consistent changes were increased relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia species and decreased abundance of Coprococcus and Eubacterium. Possible mechanisms linking the microbiota and MAFLD are increased intestinal permeability with translocation of microbial products into the portal circulation, but also changes in the bile acids and production of microbial metabolites such as ethanol, short chain fatty acids and amino acid derivatives able to modulate liver metabolism and inflammation. Several interventional studies exist that attempt to modulate liver disease by administering antibiotics, probiotics, prebiotics, synbiotics, postbiotics or fecal transplantation. In conclusion, there are both gaps and hopes concerning the interest of gut microbiome evaluation for diagnosis purposes of MAFLD and for new therapeutic developments that are often tested on small size cohorts. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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34 pages, 2485 KiB

Open AccessReview

Versatile Triad Alliance: Bile Acid, Taurine and Microbiota

by Kalina Duszka

Cells 2022, 11(15), 2337; https://doi.org/10.3390/cells11152337 - 29 Jul 2022

Cited by 29 | Viewed by 10189

Abstract

Taurine is the most abundant free amino acid in the body, and is mainly derived from the diet, but can also be produced endogenously from cysteine. It plays multiple essential roles in the body, including development, energy production, osmoregulation, prevention of oxidative stress, [...] Read more.

Taurine is the most abundant free amino acid in the body, and is mainly derived from the diet, but can also be produced endogenously from cysteine. It plays multiple essential roles in the body, including development, energy production, osmoregulation, prevention of oxidative stress, and inflammation. Taurine is also crucial as a molecule used to conjugate bile acids (BAs). In the gastrointestinal tract, BAs deconjugation by enteric bacteria results in high levels of unconjugated BAs and free taurine. Depending on conjugation status and other bacterial modifications, BAs constitute a pool of related but highly diverse molecules, each with different properties concerning solubility and toxicity, capacity to activate or inhibit receptors of BAs, and direct and indirect impact on microbiota and the host, whereas free taurine has a largely protective impact on the host, serves as a source of energy for microbiota, regulates bacterial colonization and defends from pathogens. Several remarkable examples of the interaction between taurine and gut microbiota have recently been described. This review will introduce the necessary background information and lay out the latest discoveries in the interaction of the co-reliant triad of BAs, taurine, and microbiota. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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23 pages, 1930 KiB

Open AccessReview

Obstructive Sleep Apnea as a Risk Factor for COVID-19 Severity—The Gut Microbiome as a Common Player Mediating Systemic Inflammation via Gut Barrier Dysfunction

by Saif Mashaqi, Rekha Kallamadi, Abhishek Matta, Stuart F. Quan, Salma I. Patel, Daniel Combs, Lauren Estep, Joyce Lee-Iannotti, Charles Smith, Sairam Parthasarathy and David Gozal

Cells 2022, 11(9), 1569; https://doi.org/10.3390/cells11091569 - 6 May 2022

Cited by 11 | Viewed by 4591

Abstract

The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the [...] Read more.

The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the severity of COVID-19 outcomes (such as age, hypertension, diabetes mellitus, and obesity). Since many of these risk factors are known to be influenced by obstructive sleep apnea, this raises the possibility that OSA might be an independent risk factor for COVID-19 severity. A shift in the gut microbiota has been proposed to contribute to outcomes in both COVID-19 and OSA. To further evaluate the potential triangular interrelationships between these three elements, we conducted a thorough literature review attempting to elucidate these interactions. From this review, it is concluded that OSA may be a risk factor for worse COVID-19 clinical outcomes, and the shifts in gut microbiota associated with both COVID-19 and OSA may mediate processes leading to bacterial translocation via a defective gut barrier which can then foster systemic inflammation. Thus, targeting biomarkers of intestinal tight junction dysfunction in conjunction with restoring gut dysbiosis may provide novel avenues for both risk detection and adjuvant therapy. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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27 pages, 2056 KiB

Open AccessReview

Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review

by Sharma Sonali, Bipul Ray, Hediyal Ahmed Tousif, Annan Gopinath Rathipriya, Tuladhar Sunanda, Arehally M. Mahalakshmi, Wiramon Rungratanawanich, Musthafa Mohamed Essa, M. Walid Qoronfleh, Saravana Babu Chidambaram and Byoung-Joon Song

Cells 2022, 11(8), 1362; https://doi.org/10.3390/cells11081362 - 16 Apr 2022

Cited by 64 | Viewed by 11400

Abstract

Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive [...] Read more.

Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive behaviors. The gut microbiome communicates with the brain through the neural, immune, and metabolic pathways, either directly (via vagal nerves) or indirectly (via gut- and microbial-derived metabolites as well as gut hormones and endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, and ghrelin). Maintaining healthy gut microbiota (GM) is now being recognized as important for brain health through the use of probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM and hypothalamus–pituitary–adrenal (HPA) axis functions. In this review, we have summarized the etiopathogenic link between gut dysbiosis and depression with preclinical and clinical evidence. In addition, we have collated information on the recent therapies and supplements, such as probiotics, prebiotics, short-chain fatty acids, and vitamin B12, omega-3 fatty acids, etc., which target the gut–brain axis (GBA) for the effective management of depressive behavior and anxiety. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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11 pages, 1428 KiB

Open AccessReview

Targeting the Pulmonary Microbiota to Fight against Respiratory Diseases

by Zongjie Li, Yuhao Li, Qing Sun, Jianchao Wei, Beibei Li, Yafeng Qiu, Ke Liu, Donghua Shao and Zhiyong Ma

Cells 2022, 11(5), 916; https://doi.org/10.3390/cells11050916 - 7 Mar 2022

Cited by 15 | Viewed by 4316

Abstract

The mucosal immune system of the respiratory tract possesses an effective “defense barrier” against the invading pathogenic microorganisms; therefore, the lungs of healthy organisms are considered to be sterile for a long time according to the strong pathogens-eliminating ability. The emergence of next-generation [...] Read more.

The mucosal immune system of the respiratory tract possesses an effective “defense barrier” against the invading pathogenic microorganisms; therefore, the lungs of healthy organisms are considered to be sterile for a long time according to the strong pathogens-eliminating ability. The emergence of next-generation sequencing technology has accelerated the studies about the microbial communities and immune regulating functions of lung microbiota during the past two decades. The acquisition and maturation of respiratory microbiota during childhood are mainly determined by the birth mode, diet structure, environmental exposure and antibiotic usage. However, the formation and development of lung microbiota in early life might affect the occurrence of respiratory diseases throughout the whole life cycle. The interplay and crosstalk between the gut and lung can be realized by the direct exchange of microbial species through the lymph circulation, moreover, the bioactive metabolites produced by the gut microbiota and lung microbiota can be changed via blood circulation. Complicated interactions among the lung microbiota, the respiratory viruses, and the host immune system can regulate the immune homeostasis and affect the inflammatory response in the lung. Probiotics, prebiotics, functional foods and fecal microbiota transplantation can all be used to maintain the microbial homeostasis of intestinal microbiota and lung microbiota. Therefore, various kinds of interventions on manipulating the symbiotic microbiota might be explored as novel effective strategies to prevent and control respiratory diseases. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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21 pages, 12172 KiB

Open AccessFeature PaperReview

Role of Dietary Supplements and Probiotics in Modulating Microbiota and Bone Health: The Gut-Bone Axis

by Alessandro de Sire, Roberto de Sire, Claudio Curci, Fabiana Castiglione and Walter Wahli

Cells 2022, 11(4), 743; https://doi.org/10.3390/cells11040743 - 21 Feb 2022

Cited by 54 | Viewed by 9787

Abstract

Osteoporosis is characterized by an alteration of bone microstructure with a decreased bone mineral density, leading to the incidence of fragility fractures. Around 200 million people are affected by osteoporosis, representing a major health burden worldwide. Several factors are involved in the pathogenesis [...] Read more.

Osteoporosis is characterized by an alteration of bone microstructure with a decreased bone mineral density, leading to the incidence of fragility fractures. Around 200 million people are affected by osteoporosis, representing a major health burden worldwide. Several factors are involved in the pathogenesis of osteoporosis. Today, altered intestinal homeostasis is being investigated as a potential additional risk factor for reduced bone health and, therefore, as a novel potential therapeutic target. The intestinal microflora influences osteoclasts’ activity by regulating the serum levels of IGF-1, while also acting on the intestinal absorption of calcium. It is therefore not surprising that gut dysbiosis impacts bone health. Microbiota alterations affect the OPG/RANKL pathway in osteoclasts, and are correlated with reduced bone strength and quality. In this context, it has been hypothesized that dietary supplements, prebiotics, and probiotics contribute to the intestinal microecological balance that is important for bone health. The aim of the present comprehensive review is to describe the state of the art on the role of dietary supplements and probiotics as therapeutic agents for bone health regulation and osteoporosis, through gut microbiota modulation. Full article

(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)

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