-
Antibiotics (Basel, Switzerland) Nov 2023Graft-versus-host disease (GvHD) is a severe complication after hematopoietic stem cell transplantation (HSCT). Our study focused on identifying multidrug-resistant...
High Diversity but Monodominance of Multidrug-Resistant Bacteria in Immunocompromised Pediatric Patients with Acute Lymphoblastic Leukemia Developing GVHD Are Not Associated with Changes in Gut Mycobiome.
Graft-versus-host disease (GvHD) is a severe complication after hematopoietic stem cell transplantation (HSCT). Our study focused on identifying multidrug-resistant (MDR) gut bacteria associated with GvHD-prone guts and association with gut microbiota (GM) diversity, bacteriome, and mycobiome composition in post-HSCT patients. We examined 11 pediatric patients with acute lymphoblastic leukemia (ALL), including six with GvHD, within three time points: seven days pre-HSCT, seven days post-, and 28 days post-HSCT. The gut microbiome and its resistome were investigated using metagenomic sequencing, taxonomically classified with Kraken2, and statistically evaluated for significance using appropriate tests. We observed an increase in the abundance of MDR bacteria, mainly strains carrying , , , , and genes, in GvHD patients one week post-HSCT. Conversely, non-GvHD patients had more MDR beneficial bacteria pre-HSCT, promoting immunosurveillance, with resistance genes increasing one-month post-HSCT. MDR beneficial bacteria included the anti-inflammatory , , and , while most MDR bacteria represented the dominant species of GM. Changes in the gut mycobiome were not associated with MDR bacterial monodominance or GvHD. Significant α-diversity decline (Shannon index) one week and one month post-HSCT in GvHD patients ( < 0.05) was accompanied by increased and decreased post-HSCT. Our findings suggest that MDR commensal gut bacteria may preserve diversity and enhance immunosurveillance, potentially preventing GvHD in pediatric ALL patients undergoing HSCT. This observation has therapeutic implications.
PubMed: 38136701
DOI: 10.3390/antibiotics12121667 -
Science Advances Dec 2023Emerging evidence implicates gut microbial metabolism in neurodevelopmental disorders, but its influence on typical neurodevelopment has not been explored in detail. We...
Emerging evidence implicates gut microbial metabolism in neurodevelopmental disorders, but its influence on typical neurodevelopment has not been explored in detail. We investigated the relationship between the microbiome and neuroanatomy and cognition of 381 healthy children, demonstrating that differences in microbial taxa and genes are associated with overall cognitive function and the size of brain regions. Using a combination of statistical and machine learning models, we showed that species including , , and were enriched or depleted in children with higher cognitive function scores. Microbial metabolism of short-chain fatty acids was also associated with cognitive function. In addition, machine models were able to predict the volume of brain regions from microbial profiles, and taxa that were important in predicting cognitive function were also important for predicting individual brain regions and specific subscales of cognitive function. These findings provide potential biomarkers of neurocognitive development and may enable development of targets for early detection and intervention.
Topics: Child; Humans; Neuroanatomy; Feces; Cognition; Brain; Gastrointestinal Microbiome
PubMed: 38134274
DOI: 10.1126/sciadv.adi0497 -
Rheumatology and Immunology Research Dec 2023The gut microbiome represents a potential promising therapeutic target for autoimmune diseases. This review summarizes the current knowledge on the links between the gut...
The gut microbiome represents a potential promising therapeutic target for autoimmune diseases. This review summarizes the current knowledge on the links between the gut microbiome and several autoimmune rheumatic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) spondyloarthropathies (SpA), Sjogren's syndrome (SS), and systemic sclerosis (SSc). Evidence from studies of RA and SLE patients suggests that alterations in the gut microbiome composition and function contribute to disease development and progression through increased gut permeability, with microbes and microbial metabolites driving an excessive systemic activation of the immune system. Also, there is growing evidence that gut dysbiosis and subsequent immune cell activation may contribute to disease pathogenesis in SpA and SS. For SSc, there are fewer, but these are still informative, reports on alterations in the gut microbiome. In general, the complex interplay between the microbiome and the immune system is still not fully understood. Here we discuss the current knowledge of the link between the gut microbiome and autoimmune rheumatic diseases, highlighting potentially fertile areas for future research and make considerations on the potential benefits of strategies that restore gut microbiome homeostasis.
PubMed: 38125641
DOI: 10.2478/rir-2023-0027 -
Journal of Alzheimer's Disease : JAD 2024Gut microbiota could affect the onset and development of vascular cognitive impairment (VCI) through modulating metabolic and immune pathways. However, the vascular...
BACKGROUND
Gut microbiota could affect the onset and development of vascular cognitive impairment (VCI) through modulating metabolic and immune pathways. However, the vascular mechanisms involved remain unclear.
OBJECTIVE
To investigate the gut microbiota associated with VCI and examine the mediating effects of regional cerebral blood flow (CBF) to explore potential therapeutic targets for VCI.
METHODS
This prospective study enrolled patients with VCI (n = 16) and healthy controls (n = 18) from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1 and June 30, 2022. The gut microbiota composition and diversity were determined by 16 S ribosomal RNA gene sequencing. The association between gut microbiota and Montreal Cognitive Assessment (MoCA) scores was determined using Spearman's correlation analysis. Regional CBF was calculated using pseudo-continuous arterial spin labeling. The mediating effects of regional CBF on the relationship between specific gut microbiota and cognition in VCI were investigated using mediation analysis.
RESULTS
Compared to healthy controls, patients with VCI had significantly greater abundance of Bifidobacterium, Veillonella, R uminococcus gnavus , Fusobacterium, and Erysipelatoclostridium and smaller abundance of Collinsella. The abundance of Ruminococcus gnavus was negatively associated with MoCA scores in patients with VCI, with the CBF in the left hypothalamus, right hypothalamus, and left amygdala accounting for 63.96%, 48.22%, and 36.51%, respectively, of this association after adjusting for confounders.
CONCLUSIONS
Ruminococcus gnavus is associated with cognition in VCI, which is strongly mediated by CBF in the bilateral hypothalamus and left amygdala. These findings highlight the potential regulatory roles of nutrition and metabolism-related areas of the brain in VCI.
Topics: Humans; Prospective Studies; Gastrointestinal Microbiome; Cognitive Dysfunction; Cognition; Cerebrovascular Circulation
PubMed: 38108351
DOI: 10.3233/JAD-230709 -
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 -
Physiological Genomics Mar 2024Chronic intestinal inflammation is a poorly understood manifestation of cystic fibrosis (CF), which may be refractory to ion channel CF transmembrane conductance...
Chronic intestinal inflammation is a poorly understood manifestation of cystic fibrosis (CF), which may be refractory to ion channel CF transmembrane conductance regulator (CFTR) modulator therapy. People with CF exhibit intestinal dysbiosis, which has the potential for stimulating intestinal and systemic inflammation. CFTR is expressed in organ epithelia, leukocytes, and other tissues. Here, we investigate the contribution of intestinal epithelium-specific loss of Cftr [iCftr knockout (KO)] to dysbiosis and inflammation in mice treated with either of two antiobstructive dietary regimens necessary to maintain CF mouse models [polyethylene glycol (PEG) laxative or a liquid diet (LiqD)]. Feces collected from iCftr KO mice and their wild-type (WT) sex-matched littermates were used to measure fecal calprotectin to evaluate inflammation and to perform 16S rRNA sequencing to characterize the gut microbiome. Fecal calprotectin was elevated in iCftr KO relative to WT mice that consumed either PEG or LiqD. PEG iCftr KO mice did not show a change in α diversity versus WT mice but demonstrated a significant difference in microbial composition (β diversity) with included increases in the phylum Proteobacteria, the family , four genera of including , and the mucolytic genus . Fecal microbiome analysis of LiqD-fed iCftr KO mice showed both decreased α diversity and differences in microbial composition with increases in the Proteobacteria family , Firmicutes families and , and enrichment of , , , mucolytic , and reduction of Akkermansia. It was concluded that epithelium-specific loss of Cftr is a major driver of CF intestinal dysbiosis and inflammation with significant similarities to previous studies of pan Cftr KO mice. Chronic intestinal inflammation is a manifestation of cystic fibrosis (CF), a disease caused by loss of the anion channel CF transmembrane conductance regulator (CFTR) that is expressed in many tissues. This study shows that intestinal epithelial cell-specific loss of CFTR [inducible Cftr knockout (KO)] in mice is sufficient to induce intestinal dysbiosis and inflammation. Experiments were performed on mice consuming two dietary regimens routinely used to prevent obstruction in CF mice.
Topics: Animals; Humans; Mice; Clostridioides difficile; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Dysbiosis; Expectorants; Feces; Inflammation; Intestinal Obstruction; Leukocyte L1 Antigen Complex; Mice, Inbred CFTR; Mice, Knockout; RNA, Ribosomal, 16S
PubMed: 38073491
DOI: 10.1152/physiolgenomics.00077.2023 -
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