Effects of Gut Microbiota on Human Health and Disease

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 10293

Special Issue Editor


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Guest Editor
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
Interests: animal internal medicine and toxic diseases; animal nutritional metabolic diseases and immunity; intestinal microbes; probiotic fermentation; obesity; liver fibrosis; cholestatic liver injury
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Special Issue Information

Dear Colleagues,

The intestinal microbiota may contribute to human health and disease. However, to gain a mechanistic understanding of how the gut microbiota affects human health and disease, the current research is moving away from descriptive microbiota census analyses toward cause-and-effect studies. Joint analyses of high-throughput human multi-omics data, including metagenomics and metabolomics data, together with measures of host physiology and mechanistic experiments in humans hold potential as initial steps in the identification of potential molecular mechanisms behind previously reported associations. Through this topic, we will discuss the current knowledge of how the gut microbiota and derived microbial compounds may be linked to the metabolism of the healthy human host or to the pathogenesis of common human diseases. We will highlight examples of microbiota-targeted interventions aiming to optimize metabolic health, and provide perspectives for future basic and translational investigations within this nascent and promising research field.

The aim of this Special Issue of Microorganisms is to present a collection of articles that provide a snapshot of current research into the effects of the gut microbiota on human health and disease. Manuscripts covering all aspects of research relating to this area are welcome.

Dr. Yunhuan Liu
Guest Editor

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Keywords

  • gut microbiota

  • human health
  • human disease
  • virus
  • microorganism
  • nutrition
  • metabolic disease
  • liver
  • gut
  • kidney

Published Papers (9 papers)

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Research

20 pages, 4832 KiB  
Article
Microbial Indoles: Key Regulators of Organ Growth and Metabolic Function
by Peter Yuli Xing, Ruchi Agrawal, Anusha Jayaraman, Katherine Ann Martin, George Wei Zhang, Ee Ling Ngu, Llanto Elma Faylon, Staffan Kjelleberg, Scott A. Rice, Yulan Wang, Adesola T. Bello, Elaine Holmes, Jeremy K. Nicholson, Luke Whiley and Sven Pettersson
Microorganisms 2024, 12(4), 719; https://doi.org/10.3390/microorganisms12040719 - 02 Apr 2024
Viewed by 699
Abstract
Gut microbes supporting body growth are known but the mechanisms are less well documented. Using the microbial tryptophan metabolite indole, known to regulate prokaryotic cell division and metabolic stress conditions, we mono-colonized germ-free (GF) mice with indole-producing wild-type Escherichia coli (E. coli [...] Read more.
Gut microbes supporting body growth are known but the mechanisms are less well documented. Using the microbial tryptophan metabolite indole, known to regulate prokaryotic cell division and metabolic stress conditions, we mono-colonized germ-free (GF) mice with indole-producing wild-type Escherichia coli (E. coli) or tryptophanase-encoding tnaA knockout mutant indole-non-producing E. coli. Indole mutant E. coli mice showed multiorgan growth retardation and lower levels of glycogen, cholesterol, triglycerides, and glucose, resulting in an energy deficiency despite increased food intake. Detailed analysis revealed a malfunctioning intestine, enlarged cecum, and reduced numbers of enterochromaffin cells, correlating with a metabolic phenotype consisting of impaired gut motility, diminished digestion, and lower energy harvest. Furthermore, indole mutant mice displayed reduction in serum levels of tricarboxylic acid (TCA) cycle intermediates and lipids. In stark contrast, a massive increase in serum melatonin was observed—frequently associated with accelerated oxidative stress and mitochondrial dysfunction. This observational report discloses functional roles of microbe-derived indoles regulating multiple organ functions and extends our previous report of indole-linked regulation of adult neurogenesis. Since indoles decline by age, these results imply a correlation with age-linked organ decline and levels of indoles. Interestingly, increased levels of indole-3-acetic acid, a known indole metabolite, have been shown to correlate with younger biological age, further supporting a link between biological age and levels of microbe-derived indole metabolites. The results presented in this resource paper will be useful for the future design of food intervention studies to reduce accelerated age-linked organ decline. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease)
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11 pages, 596 KiB  
Article
Association between Gut Microbiota and Muscle Strength in Japanese General Population of the Iwaki Health Promotion Project
by Yoshikuni Sugimura, Yichi Yang, Akira Kanda, Akihiro Mawatari, Yoshinori Tamada, Tatsuya Mikami, Shigeyuki Nakaji and Kazushige Ihara
Microorganisms 2024, 12(3), 622; https://doi.org/10.3390/microorganisms12030622 - 20 Mar 2024
Viewed by 649
Abstract
The association between the gut microbiota and muscle strength has garnered attention in the context of mitigating muscle decline. However, many study subjects have been individuals with existing illnesses or the elderly only. This study aims to elucidate the association between the gut [...] Read more.
The association between the gut microbiota and muscle strength has garnered attention in the context of mitigating muscle decline. However, many study subjects have been individuals with existing illnesses or the elderly only. This study aims to elucidate the association between the gut microbiota and muscle strength indicators using grip strength/BMI in a large-scale study of community residents. The mean age of men (n = 442) and women (n = 588) was 50.5 (15.3) and 51.2 (15.9) years, respectively. The muscle strength indicator used was grip/BMI. The association between total read count and genus-level gut microbiota and muscle strength was analyzed. The mean grip/BMI was 1.8 (0.3) for men and 1.2 (0.2) for women. The genus of the gut microbiota that showed an association in both sexes was Eggerthella (men: β = 0.18, CI: 0.04–0.31, p = 0.009; women: β = 0.07, CI: 0.00–0.12, p = 0.028). Blautia, Eggerthella and Faecalibacterium were found to be significantly associated with grip/BMI in both the multiple regression analysis and Spearman’s correlation analysis after the multiple comparison adjustment. These results suggest that an increase in Blautia and Eggerthella, coupled with a decrease in Faecalibacterium, may contribute to muscle strengthening or the suppression of muscle weakness. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease)
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25 pages, 2954 KiB  
Article
Changes in Bacterial Gut Composition in Parkinson’s Disease and Their Metabolic Contribution to Disease Development: A Gut Community Reconstruction Approach
by Johanna Forero-Rodríguez, Johannes Zimmermann, Jan Taubenheim, Natalia Arias-Rodríguez, Juan David Caicedo-Narvaez, Lena Best, Cindy V. Mendieta, Julieth López-Castiblanco, Laura Alejandra Gómez-Muñoz, Janneth Gonzalez-Santos, Humberto Arboleda, William Fernandez, Christoph Kaleta and Andrés Pinzón
Microorganisms 2024, 12(2), 325; https://doi.org/10.3390/microorganisms12020325 - 04 Feb 2024
Viewed by 1762
Abstract
Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease with the major symptoms comprising loss of movement coordination (motor dysfunction) and non-motor dysfunction, including gastrointestinal symptoms. Alterations in the gut microbiota composition have been reported in PD patients vs. controls. However, it [...] Read more.
Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease with the major symptoms comprising loss of movement coordination (motor dysfunction) and non-motor dysfunction, including gastrointestinal symptoms. Alterations in the gut microbiota composition have been reported in PD patients vs. controls. However, it is still unclear how these compositional changes contribute to disease etiology and progression. Furthermore, most of the available studies have focused on European, Asian, and North American cohorts, but the microbiomes of PD patients in Latin America have not been characterized. To address this problem, we obtained fecal samples from Colombian participants (n = 25 controls, n = 25 PD idiopathic cases) to characterize the taxonomical community changes during disease via 16S rRNA gene sequencing. An analysis of differential composition, diversity, and personalized computational modeling was carried out, given the fecal bacterial composition and diet of each participant. We found three metabolites that differed in dietary habits between PD patients and controls: carbohydrates, trans fatty acids, and potassium. We identified six genera that changed significantly in their relative abundance between PD patients and controls, belonging to the families Lachnospiraceae, Lactobacillaceae, Verrucomicrobioaceae, Peptostreptococcaceae, and Streptococcaceae. Furthermore, personalized metabolic modeling of the gut microbiome revealed changes in the predicted production of seven metabolites (Indole, tryptophan, fructose, phenylacetic acid, myristic acid, 3-Methyl-2-oxovaleric acid, and N-Acetylneuraminic acid). These metabolites are associated with the metabolism of aromatic amino acids and their consumption in the diet. Therefore, this research suggests that each individual’s diet and intestinal composition could affect host metabolism. Furthermore, these findings open the door to the study of microbiome–host interactions and allow us to contribute to personalized medicine. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease)
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14 pages, 1761 KiB  
Article
Polyethylene Terephthalate Hydrolases in Human Gut Microbiota and Their Implications for Human Health
by Heqi Zhou, Songbiao Shi, Qiuhong You, Kaikai Zhang, Yuchuan Chen, Dekai Zheng and Jian Sun
Microorganisms 2024, 12(1), 138; https://doi.org/10.3390/microorganisms12010138 - 10 Jan 2024
Viewed by 1148
Abstract
Polyethylene terephthalate (PET), primarily utilized for food and beverage packaging, consistently finds its way into the human gut, thereby exerting adverse effects on human health. PET hydrolases, critical for the degradation of PET, have been predominantly sourced from environmental microbial communities. Given the [...] Read more.
Polyethylene terephthalate (PET), primarily utilized for food and beverage packaging, consistently finds its way into the human gut, thereby exerting adverse effects on human health. PET hydrolases, critical for the degradation of PET, have been predominantly sourced from environmental microbial communities. Given the fact that the human gut harbors a vast and intricate consortium of microorganisms, inquiry into the presence of potential PET hydrolases within the human gut microbiota becomes imperative. In this investigation, we meticulously screened 22,156 homologous sequences that could potentially encode PET hydrolases using the hidden Markov model (HMM) paradigm, drawing from 4984 cultivated genomes of healthy human gut bacteria. Subsequently, we methodically validated the hydrolytic efficacy of five selected candidate PET hydrolases on both PET films and powders composed of micro-plastics (MPs). Notably, our study also unveiled the influence of both diverse PET MP powders and their resultant hydrolysates on the modulation of cytokine expression in macrophages. In summary, our research underscores the ubiquitous prevalence and considerable potential of the human gut microbiota in PET hydrolysis. Furthermore, our study significantly contributes to the holistic evaluation of the potential health hazards posed by PET MPs to human well-being. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease)
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14 pages, 2289 KiB  
Article
The Impact of Intestinal Microbiota and Toll-like Receptor 2 Signaling on α-Synuclein Pathology in Nontransgenic Mice Injected with α-Synuclein Preformed Fibrils
by Yukako Koyanagi, Momoe Kassai and Hiroshi Yoneyama
Microorganisms 2024, 12(1), 106; https://doi.org/10.3390/microorganisms12010106 - 05 Jan 2024
Viewed by 870
Abstract
Intestinal microbiota and Toll-like receptor 2 (TLR2), which can bind lipoteichoic acid produced by microbiota, might contribute to the pathogenesis of Parkinson’s disease (PD), which is characterized by α-synuclein accumulation. Although the contribution of intestinal microbiota and TLR2 to PD pathology was validated [...] Read more.
Intestinal microbiota and Toll-like receptor 2 (TLR2), which can bind lipoteichoic acid produced by microbiota, might contribute to the pathogenesis of Parkinson’s disease (PD), which is characterized by α-synuclein accumulation. Although the contribution of intestinal microbiota and TLR2 to PD pathology was validated in genetic PD models, evidence suggests that the effects of TLR2 signaling on proteinopathy might depend on the presence of a genetic etiology. We examined the impact of intestinal microbiota and TLR2 signaling on α-synuclein pathology in a nontransgenic mouse model of sporadic PD. While an α-synuclein preformed fibrils injection successfully reproduced PD pathology by inducing accumulation of α-synuclein aggregates, microglial activation and increased TLR2 expression in the brains of nontransgenic mice, antibiotic-induced reduction in the density of intestinal microbiota and TLR2 knockout had small impact on these changes. These findings, which are in contrast to those reported in transgenic mice harboring transgene encoding α-synuclein, indicate that the contribution of intestinal microbiota and TLR2 signaling to α-synuclein pathogenesis might be influenced by the presence of a genetic etiology. Additionally, these findings suggest that integrating insights from this experimental model and genetic models would further advance our understanding of the molecular mechanisms underlying sporadic PD. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease)
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15 pages, 2172 KiB  
Article
Comparative Study of Intestinal Microbiome in Patients with Ulcerative Colitis and Healthy Controls in Korea
by Kyung-Hyo Do, Seung-Hyun Ko, Ki Bae Kim, Kwangwon Seo and Wan-Kyu Lee
Microorganisms 2023, 11(11), 2750; https://doi.org/10.3390/microorganisms11112750 - 11 Nov 2023
Viewed by 857
Abstract
Ulcerative colitis (UC) poses a contemporary medical challenge, with its exact cause still eluding researchers. This is due to various factors, such as the rising incidence, diagnostic complexities, and difficulties associated with its management. We compared the intestinal microbiome of patients with UC [...] Read more.
Ulcerative colitis (UC) poses a contemporary medical challenge, with its exact cause still eluding researchers. This is due to various factors, such as the rising incidence, diagnostic complexities, and difficulties associated with its management. We compared the intestinal microbiome of patients with UC to that of healthy controls to determine the qualitative and quantitative changes associated with UC that occur in the intestinal microbiota. The intestinal bacterial abundance in 40 Korean patients with UC and 25 healthy controls was assayed using via next-generation sequencing. There were five major phyla in both groups: Firmicutes (UC patients: 51.12%; healthy controls: 46.90%), Bacteroidota (UC patients: 37.04%; healthy controls: 40.34%), Proteobacteria (UC patients: 6.01%; healthy controls: 11.05%), Actinobacteriota (UC patients: 5.71%; healthy controls: 1.56%), and Desulfobacteriota (UC patients: 0.13%; healthy controls: 0.14%). Firmicutes was more prevalent in patients with UC (51.12%) compared to that of healthy controls (46.90%). Otherwise, Bacteroidota was more prevalent in healthy controls (40.34%) compared to patients with UC (37.04%). Although there was no significant difference, our results showed a substantially lower gut microbiome diversity in patients with UC (mean: 16.5; 95% confidence interval (CI) = 14.956–18.044) than in healthy controls (mean: 17.84; 95% CI = 15.989–19.691), the beta diversity and the flora structure of the microbiome in patients with UC differed from those in healthy controls. This will be helpful for the development of new treatment options and lay the groundwork for future research on UC. To understand the disease mechanism, it is essential to define the different types of microbes in the guts of patients with UC. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease)
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12 pages, 3489 KiB  
Article
The Dynamic Changes in the Composition and Diversity of Vaginal Microbiota in Women of Different Pregnancy Periods
by Feifei Hu, Xin Sun, Yao Su and Mingli Huang
Microorganisms 2023, 11(11), 2686; https://doi.org/10.3390/microorganisms11112686 - 02 Nov 2023
Viewed by 941
Abstract
The vaginal microbiota undergoes subtle changes during pregnancy, which may affect different pregnancy responses. This study used the Illumina MiSeq high-throughput sequencing method to analyze the 16S rRNA gene amplicons of pregnant women and the vaginal microbiota structure of pregnant women at different [...] Read more.
The vaginal microbiota undergoes subtle changes during pregnancy, which may affect different pregnancy responses. This study used the Illumina MiSeq high-throughput sequencing method to analyze the 16S rRNA gene amplicons of pregnant women and the vaginal microbiota structure of pregnant women at different pregnancy periods. There were a total of 15 pregnant women, with 45 samples were taken from these women, within half a year before becoming pregnant, in the last trimester, and 42 days postpartum. Before and after pregnancy, the female vaginal microbiota was mainly composed of Firmicutes, followed by Actinobacteriota and Proteobacteria. The abundance of Lactobacillus was relatively high. The α-diversity and microbial abundance were relatively low, and there was no significant difference in microbial composition between the two. After childbirth, the diversity and abundance of women’s vaginal bacterial communities were higher, with a decrease in the number of Firmicutes and a higher abundance of Actinobacteria, Proteobacteria, and Bacteroidota. There was a significant difference in the microbial community structure before and after pregnancy. This study showed that the microbiota structure of the vagina of pregnant women was similar to before pregnancy, but after childbirth, there were significant changes in the microbiota of the vagina, with a decrease in the number of probiotics and an increase in the number of harmful bacteria, increasing the risk of illness. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease)
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15 pages, 1315 KiB  
Article
Gut Microbiota Associated with Clostridioides difficile Carriage in Three Clinical Groups (Inflammatory Bowel Disease, C. difficile Infection and Healthcare Workers) in Hospital Field
by Elisa Martinez, Sebastien Crevecoeur, Carine Thirion, Jessica Grandjean, Papa Abdoulaye Fall, Marie-Pierre Hayette, Moutschen Michel, Bernard Taminiau, Edouard Louis and Georges Daube
Microorganisms 2023, 11(10), 2527; https://doi.org/10.3390/microorganisms11102527 - 10 Oct 2023
Viewed by 988
Abstract
Clostridioides difficile is an anaerobic spore-forming Gram-positive bacterium. C. difficile carriage and 16S rDNA profiling were studied in three clinical groups at three different sampling times: inflammatory bowel disease (IBD) patients, C. difficile infection (CDI) patients and healthcare workers (HCWs). Diversity analysis was [...] Read more.
Clostridioides difficile is an anaerobic spore-forming Gram-positive bacterium. C. difficile carriage and 16S rDNA profiling were studied in three clinical groups at three different sampling times: inflammatory bowel disease (IBD) patients, C. difficile infection (CDI) patients and healthcare workers (HCWs). Diversity analysis was realized in the three clinical groups, the positive and negative C. difficile carriage groups and the three analysis periods. Concerning the three clinical groups, β-diversity tests showed significant differences between them, especially between the HCW group and IBD group and between IBD patients and CDI patients. The Simpson index (evenness) showed a significant difference between two clinical groups (HCWs and IBD). Several genera were significantly different in the IBD patient group (Sutterella, Agathobacter) and in the CDI patient group (Enterococcus, Clostridioides). Concerning the positive and negative C. difficile carriage groups, β-diversity tests showed significant differences. Shannon, Simpson and InvSimpson indexes showed significant differences between the two groups. Several genera had significantly different relative prevalences in the negative group (Agathobacter, Sutterella, Anaerostipes, Oscillospira) and the positive group (Enterococcus, Enterobacteriaceae_ge and Enterobacterales_ge). A microbiota footprint was detected in C. difficile-positive carriers. More experiments are needed to test this microbiota footprint to see its impact on C. difficile infection. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease)
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13 pages, 2551 KiB  
Article
Predicting Adverse Recanalization Therapy Outcomes in Acute Ischemic Stroke Patients Using Characteristic Gut Microbiota
by Ping-Song Chou, Wei-Chun Hung, I-Hsiao Yang, Chia-Ming Kuo, Meng-Ni Wu, Tzu-Chao Lin, Yi-On Fong, Chi-Hung Juan and Chiou-Lian Lai
Microorganisms 2023, 11(8), 2016; https://doi.org/10.3390/microorganisms11082016 - 05 Aug 2023
Viewed by 1425
Abstract
Recanalization therapy is the most effective treatment for eligible patients with acute ischemic stroke (AIS). Gut microbiota are involved in the pathological mechanisms and outcomes of AIS. However, the association of gut microbiota features with adverse recanalization therapy outcomes remains unclear. Herein, we [...] Read more.
Recanalization therapy is the most effective treatment for eligible patients with acute ischemic stroke (AIS). Gut microbiota are involved in the pathological mechanisms and outcomes of AIS. However, the association of gut microbiota features with adverse recanalization therapy outcomes remains unclear. Herein, we investigated gut microbiota features associated with neurological deficits in patients with AIS after recanalization therapy and whether they predict the patients’ functional outcomes. We collected fecal samples from 51 patients with AIS who received recanalization therapy and performed 16S rRNA gene sequencing (V3–V4). We compared the gut microbiota diversity and community composition between mild to moderate and severe disability groups. Next, the characteristic gut microbiota was compared between groups, and we noted that the characteristic gut microbiota in patients with mild to moderate disability included Bilophila, Butyricimonas, Oscillospiraceae_UCG-003, and Megamonas. Moreover, the relative abundance of Bacteroides fragilis, Fusobacterium sp., and Parabacteroides gordonii was high in patients with severe disability. The characteristic gut microbiota was correlated with neurological deficits, and areas under the receiver operating characteristic curves confirmed that the characteristic microbiota predicted adverse recanalization therapy outcomes. In conclusion, gut microbiota characteristics are correlated with recanalization therapy outcomes in patients with AIS. Gut microbiota may thus be a promising biomarker associated with early neurological deficits and predict recanalization therapy outcomes. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease)
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