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Frontiers in Nutrition 2023Dietary fiber improves intestinal environments, by, among others, increasing stool frequency. Kale is a good source of dietary fiber and minerals; however, the effects...
Dietary fiber improves intestinal environments, by, among others, increasing stool frequency. Kale is a good source of dietary fiber and minerals; however, the effects of kale on the intestinal environment have not yet been evaluated. This study determined how the intestinal environment, including the intestinal microbiota and its metabolome, and stool frequency are affected by the consumption of kale, in humans. A randomized controlled crossover trial, with a 4-week consumption of kale or control food, was conducted. An integrated analysis of the intestinal microbiota and metabolome was performed, and their relationship with improvements in stool frequency was analyzed. Kale intake for 4 weeks significantly increased stool frequency and altered some intestinal microbes, such as an increase in the [] group and a decrease in the [] group. Analysis of subjects with increased stool frequency revealed that this group had smaller amounts of stool before kale intake. Our findings indicate that kale modifies certain gut microbes, such as [] and [] , and improves bowel movements, particularly in those with smaller stool amounts.
PubMed: 38094924
DOI: 10.3389/fnut.2023.1247683 -
Cellular and Molecular Gastroenterology... 2024A long immune-tolerant (IT) phase lasting for decades and delayed HBeAg seroconversion (HBe-SC) in patients with chronic hepatitis B (CHB) increase the risk of liver...
BACKGROUND & AIMS
A long immune-tolerant (IT) phase lasting for decades and delayed HBeAg seroconversion (HBe-SC) in patients with chronic hepatitis B (CHB) increase the risk of liver diseases. Early entry into the immune-active (IA) phase and HBe-SC confers a favorable clinical outcome with an unknown mechanism. We aimed to identify factor(s) triggering IA entry and HBe-SC in the natural history of CHB.
METHODS
To study the relevance of gut microbiota evolution in the risk of CHB activity, fecal samples were collected from CHB patients (n = 102) in different disease phases. A hepatitis B virus (HBV)-hydrodynamic injection (HDI) mouse model was therefore established in several mouse strains and germ-free mice, and multiplatform metabolomic and bacteriologic assays were performed.
RESULTS
Ruminococcus gnavus was the most abundant species in CHB patients in the IT phase, whereas Akkermansia muciniphila was predominantly enriched in IA patients and associated with alanine aminotransferase flares, HBeAg loss, and early HBe-SC. HBV-HDI mouse models recapitulated this human finding. Increased cholesterol-to-bile acids (BAs) metabolism was found in IT patients because R gnavus encodes bile salt hydrolase to deconjugate primary BAs and augment BAs total pool for facilitating HBV persistence and prolonging the IT course. A muciniphila counteracted this activity through the direct removal of cholesterol. The secretome metabolites of A muciniphila, which contained small molecules structurally similar to apigenin, lovastatin, ribavirin, etc., inhibited the growth and the function of R gnavus to allow HBV elimination.
CONCLUSIONS
R gnavus and A muciniphila play opposite roles in HBV infection. A muciniphila metabolites, which benefit the elimination of HBV, may contribute to future anti-HBV strategies.
Topics: Animals; Humans; Mice; Akkermansia; Cholesterol; Clostridiales; Hepatitis B e Antigens; Hepatitis B, Chronic; Gastrointestinal Microbiome
PubMed: 38092311
DOI: 10.1016/j.jcmgh.2023.12.003 -
Frontiers in Immunology 2023Adenoid hypertrophy (AH) is a common upper respiratory disorder in children. Disturbances of gut microbiota have been implicated in AH. However, the interplay of...
INTRODUCTION
Adenoid hypertrophy (AH) is a common upper respiratory disorder in children. Disturbances of gut microbiota have been implicated in AH. However, the interplay of alteration of gut microbiome and enlarged adenoids remains elusive.
METHODS
119 AH children and 100 healthy controls were recruited, and microbiome profiling of fecal samples in participants was performed using 16S rRNA gene sequencing. Fecal microbiome transplantation (FMT) was conducted to verify the effects of gut microbiota on immune response in mice.
RESULTS
In AH individuals, only a slight decrease of diversity in bacterial community was found, while significant changes of microbial composition were observed between these two groups. Compared with HCs, decreased abundances of , and genera and increased abundances of , , genera were revealed in AH patients. The abundance of remained stable with age in AH children. Notably, a microbial marker panel of 8 OTUs were identified, which discriminated AH from HC individuals with an area under the curve (AUC) of 0.9851 in the discovery set, and verified in the geographically different validation set, achieving an AUC of 0.9782. Furthermore, transfer of mice with fecal microbiota from AH patients dramatically reduced the proportion of Treg subsets within peripheral blood and nasal-associated lymphoid tissue (NALT) and promoted the expansion of Th2 cells in NALT.
CONCLUSION
These findings highlight the effect of the altered gut microbiota in the AH pathogenesis.
Topics: Child; Humans; Animals; Mice; Gastrointestinal Microbiome; Adenoids; RNA, Ribosomal, 16S; Microbiota; Hypertrophy; Bacteroides
PubMed: 38090578
DOI: 10.3389/fimmu.2023.1277351 -
BMC Microbiology Dec 2023Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but...
BACKGROUND
Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted.
METHODS
We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients' fecal supernatants exposed to the QGP-1 cell model in vitro.
RESULTS
Our study demonstrated that patient's constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients' fecal supernatants increased 5-HT biosynthesis in QGP-1 cells.
CONCLUSION
FMT can relieve patients' constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.
Topics: Humans; Fecal Microbiota Transplantation; Depression; Multiomics; Serotonin; Constipation; Feces; Gastrointestinal Diseases; Anxiety
PubMed: 38057705
DOI: 10.1186/s12866-023-03123-1 -
Frontiers in Immunology 2023Gut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing...
INTRODUCTION
Gut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing on susceptibility to KD. This study aimed to evaluate whether dysbiosis elevates susceptibility to KD by assessing children with a history of KD.
METHODS
Fecal DNA was extracted from 26 children with a history of KD approximately 1 year prior (KD group, 12 boys; median age, 32.5 months; median time from onset, 11.5 months) and 57 age-matched healthy controls (HC group, 35 boys; median age, 36.0 months). 16S rRNA gene analysis was conducted with the Illumina Miseq instrument. Sequence reads were analyzed using QIIME2.
RESULTS
For alpha diversity, Faith's phylogenetic diversity was significantly higher in the KD group. Regarding beta diversity, the two groups formed significantly different clusters based on Bray-Curtis dissimilarity. Comparing microbial composition at the genus level, the KD and HC groups were significantly different in the abundance of two genera with abundance over 1% after Benjamini-Hochberg false discovery rate correction for multiple comparisons. Compared with the HC group, the KD group had higher relative abundance of group and lower relative abundance of .
DISCUSSION AND CONCLUSION
group reportedly includes pro-inflammatory bacteria. In contrast, suppresses inflammation via butyrate production. In the predictive functional analysis, the proportion of gut microbiota involved in several pathways was lower in the KD group. Therefore, dysbiosis characterized by distinct microbial diversity and decreased abundance of in parallel with increased abundance of group might be a susceptibility factor for KD.
Topics: Male; Child; Humans; Child, Preschool; Gastrointestinal Microbiome; Dysbiosis; RNA, Ribosomal, 16S; Mucocutaneous Lymph Node Syndrome; Phylogeny; Acute Disease; Ruminococcus
PubMed: 38022552
DOI: 10.3389/fimmu.2023.1268453 -
Renal Failure 2023Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of... (Review)
Review
BACKGROUND
Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of the gut microbiota in individuals with LN have not been fully clarified.
METHODS
The PubMed, Web of Science, and Embase databases were systematically searched for clinical and animal studies related to the relationship between LN and gut microbiota from inception until October 1, 2023. A semiquantitative analysis was used to assess the changes in gut microbial profiles.
RESULTS
A total of 15 clinical studies were selected for analysis, which included 138 LN patients, 441 systemic lupus erythematosus patients, and 1526 healthy controls (HCs). Five different types of LN mouse models were included in 5 animal studies. The alpha diversity was decreased in LN patients compared to HCs. A significant decrease in the (F/B) ratio is considered a hallmark of pathological conditions. Specifically, alterations in the abundance of the phylum , genera and and species and may play a critical role in the pathogenesis of LN. Remarkably, the gut taxonomic chain -- was enriched in LN patients, which could be a crucial characteristic of LN patients. The increased level of interleukin-6, imbalance of regulatory T cells and T helper 17 cells, and decreased level of the intestinal tight junction proteins zonula occludens-1 and claudin-1 also might be related to the pathogenesis of LN.
CONCLUSIONS
Specific changes in the abundance of gut microbiota such as decreased F/B ratio, and the level of inflammatory indicators, and markers of intestinal barrier dysfunction may play a crucial role in the pathogenesis of LN. These factors could be effective diagnostic and potential therapeutic targets for LN.
Topics: Animals; Mice; Humans; Lupus Nephritis; Gastrointestinal Microbiome; Lupus Erythematosus, Systemic; Intestinal Diseases; Interleukin-6
PubMed: 37994423
DOI: 10.1080/0886022X.2023.2285877 -
Scientific Reports Nov 2023To investigate the gut microbiota distribution and its functions in children with avoidant/restrictive food intake disorder (ARFID). A total of 135 children were...
To investigate the gut microbiota distribution and its functions in children with avoidant/restrictive food intake disorder (ARFID). A total of 135 children were enrolled in the study, including 102 children with ARFID and 33 healthy children. Fecal samples were analyzed to explore differences in gut microbiota composition and diversity and functional differences between the ARFID and healthy control (HC) groups via 16S rDNA and metagenomic sequencing. The gut microbiota composition and diversity in children with ARFID were different from those in heathy children, but there is no difference in the composition and diversity of gut microbiota between children at the age of 3-6 and 7-12 with ARFID. At the phylum level, the most abundant microbes in the two groups identified by 16S rDNA and metagenomic sequencing were the same. At the genus level, the abundance of Bacteroides was higher in the ARFID group (P > 0.05); however, different from the result of 16SrDNA sequencing, metagenomic sequencing showed that the abundance of Bacteroides in the ARFID group was significantly higher than that in the HC group (P = 0.041). At the species level, Escherichia coli, Streptococcus thermophilus and Lachnospira eligens were the most abundant taxa in the ARFID group, and Prevotella copri, Bifidobacterium pseudocatenulatum, and Ruminococcus gnavus were the top three microbial taxa in the HC group; there were no statistically significant differences between the abundance of these microbial taxa in the two groups. LefSe analysis indicated a greater abundance of the order Enterobacterales and its corresponding family Enterobacteriaceae, the family Bacteroidaceae and corresponding genus Bacteroides, the species Bacteroides vulgatus in ARFID group, while the abundance of the phylum Actinobacteriota and its corresponding class Actinobacteria , the order Bifidobacteriales and corresponding family Bifidobacteriaceae, the genus Bifidobacterium were enriched in the HC group. There were no statistically significant differences in the Chao1, Shannon and Simpson indices between the Y1 and Y2 groups (P = 0.1, P = 0.06, P = 0.06). At the phylum level, Bacillota, Bacteroidota, Proteobacteria and Actinobacteriota were the most abundant taxa in both groups, but there were no statistically significant differences among the abundance of these bacteria (P = 0.958, P = 0.456, P = 0.473, P = 0.065). At the genus level, Faecalibacterium was more abundant in the Y2 group than in the Y1 group, and the difference was statistically significant (P = 0.037). The KEGG annotation results showed no significant difference in gut microbiota function between children with ARFID and healthy children; however, GT26 was significantly enriched in children with ARFID based on the CAZy database. The most abundant antibiotic resistance genes in the ARFID group were the vanT, tetQ, adeF, ermF genes, and the abundance of macrolide resistance genes in the ARFID group was significantly higher than that in the HC group (P = 0.041). Compared with healthy children, children with ARFID have a different distribution of the gut microbiota and functional genes. This indicates that the gut microbiome might play an important role in the pathogenesis of ARFID.Clinical trial registration: ChiCTR2300074759.
Topics: Humans; Child; Anti-Bacterial Agents; Avoidant Restrictive Food Intake Disorder; Drug Resistance, Bacterial; Macrolides; Microbiota; Bacteria; Actinobacteria; Eating; RNA, Ribosomal, 16S
PubMed: 37985845
DOI: 10.1038/s41598-023-47760-y -
Translational Psychiatry Nov 2023Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently...
Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Two-, eight- and twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD.
Topics: Adult; Humans; Microbiota; Stress Disorders, Post-Traumatic; Gastrointestinal Microbiome; Feces; Biological Availability
PubMed: 37980332
DOI: 10.1038/s41398-023-02643-8 -
Nature Communications Nov 2023The early-life gut microbiome development has long-term health impacts and can be influenced by factors such as infant diet. Human milk oligosaccharides (HMOs), an...
The early-life gut microbiome development has long-term health impacts and can be influenced by factors such as infant diet. Human milk oligosaccharides (HMOs), an essential component of breast milk that can only be metabolized by some beneficial gut microorganisms, ensure proper gut microbiome establishment and infant development. However, how HMOs are metabolized by gut microbiomes is not fully elucidated. Isolate studies have revealed the genetic basis for HMO metabolism, but they exclude the possibility of HMO assimilation via synergistic interactions involving multiple organisms. Here, we investigate microbiome responses to 2'-fucosyllactose (2'FL), a prevalent HMO and a common infant formula additive, by establishing individualized microbiomes using fecal samples from three infants as the inocula. Bifidobacterium breve, a prominent member of infant microbiomes, typically cannot metabolize 2'FL. Using metagenomic data, we predict that extracellular fucosidases encoded by co-existing members such as Ruminococcus gnavus initiate 2'FL breakdown, thus critical for B. breve's growth. Using both targeted co-cultures and by supplementation of R. gnavus into one microbiome, we show that R. gnavus can promote extensive growth of B. breve through the release of lactose from 2'FL. Overall, microbiome cultivation combined with genome-resolved metagenomics demonstrates that HMO utilization can vary with an individual's microbiome.
Topics: Female; Child; Humans; Infant; Bifidobacterium; Trisaccharides; Milk, Human; Oligosaccharides; Microbiota
PubMed: 37973815
DOI: 10.1038/s41467-023-43279-y -
BioRxiv : the Preprint Server For... Oct 2023In metagenomics, the pool of uncharacterized microbial enzymes presents a challenge for functional annotation. Among these, carbohydrate-active enzymes (CAZymes) stand...
In metagenomics, the pool of uncharacterized microbial enzymes presents a challenge for functional annotation. Among these, carbohydrate-active enzymes (CAZymes) stand out due to their pivotal roles in various biological processes related to host health and nutrition. Here, we present CAZyLingua, the first tool that harnesses protein language model embeddings to build a deep learning framework that facilitates the annotation of CAZymes in metagenomic datasets. Our benchmarking results showed on average a higher F1 score (reflecting an average of precision and recall) on the annotated genomes of , and compared to the traditional sequence homology-based method in dbCAN2. We applied our tool to a paired mother/infant longitudinal dataset and revealed unannotated CAZymes linked to microbial development during infancy. When applied to metagenomic datasets derived from patients affected by fibrosis-prone diseases such as Crohn's disease and IgG4-related disease, CAZyLingua uncovered CAZymes associated with disease and healthy states. In each of these metagenomic catalogs, CAZyLingua discovered new annotations that were previously overlooked by traditional sequence homology tools. Overall, the deep learning model CAZyLingua can be applied in combination with existing tools to unravel intricate CAZyme evolutionary profiles and patterns, contributing to a more comprehensive understanding of microbial metabolic dynamics.
PubMed: 37961379
DOI: 10.1101/2023.10.23.563620