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FMT from IBS-D Rats Impairs Intestinal Barrier Function and is Associated with Increased Intestinal Benzoic Acid and Ruminococcus Abundance.
While the etiology of diarrhea-predominant irritable bowel syndrome (IBS-D) is multifactorial, current studies have converged to identify gut microbiota dysbiosis as a principal contributor. This study aimed to elucidate the role of the gut microbiota in IBS-D progression and to uncover the underlying mechanisms. In this study, a rat model of IBS-D was successfully established, characterized by prominent visceral hypersensitivity and diarrhea. To assess the impact of the gut microbiota, recipient rats pretreated with broad-spectrum antibiotics underwent fecal microbiota transplantation (FMT) from IBS-D model rats. The model-microbiota recipient rats (the MR group) developed IBS-D-like symptoms, such as abdominal pain, diarrhea, and depression-like behaviors. Both the IBS-D and MR groups exhibited elevated serum diamine oxidase (DAO) concentrations, reduced intestinal tight junction protein levels, increased serum TNF-α concentrations, upregulated TNF-α mRNA expression, and downregulated IL-10 mRNA expression in the intestine. These findings indicated that the transplanted microbiota disrupted intestinal barrier integrity and triggered low-grade inflammation. Moreover, an elevated abundance of Ruminococcaceae in the gut microbiota was a common feature of both the IBS-D and MR groups. Metabolomic analysis revealed an enrichment in the phenylalanine, tyrosine, and tryptophan biosynthesis pathway in both IBS-D and recipient groups, with benzoic acid being particularly prominent. Pearson correlation analysis demonstrated a strong positive correlation between the Ruminococcus abundance and benzoic acid levels. Together, these findings indicated that FMT robustly recapitulated core IBS-D pathophysiology in recipient rats, and the identified bacteria and metabolites provided novel insights into the pathogenesis of IBS-D.
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Sex-based differences in fecal short-chain fatty acid and gut microbiota in irritable bowel syndrome patients.
OBJECTIVE: To explore alterations in fecal short-chain fatty acids (SCFA) and gut microbiota in patients with diarrhea-predominant irritable bowel disease (IBS-D) and their relationships with clinical manifestations. METHODS: We recruited 162 patients with IBS-D and 66 healthy controls (HC). Their manifestations and psychological status were evaluated using the IBS severity scoring system and the Hospital Anxiety and Depression Scale (HADS). Colorectal visceral sensitivity was evaluated using a barostat. Systemic inflammation was evaluated using plasma cytokine levels. Fecal SCFA were quantified using ultra-performance liquid chromatography-tandem mass spectrometry, and fecal microbiota communities were analyzed using 16S rRNA sequencing. RESULTS: More men presented with IBS-D than women in our patient cohort. Patients with IBS-D had more severe manifestations, higher HADS score, and a higher rate of previous infectious enteritis than HC. Notably, female patients had significantly higher HADS scores than male patients. Male patients had significantly higher levels of plasma interleukin (IL)-12, fecal propionate and colorectal visceral sensitivity than male HC, while no differences were observed between female patients and female HC. Fecal acetate, butyrate and valerate correlated with the initial visceral sensory threshold, stressors, and IL-10 and IL-12 levels. The propionate-producing Prevotella 9 genus was significantly increased in male patients and positively correlated with fecal propionate. CONCLUSION: Distinct sex-based differences in clinical manifestations, fecal SCFA and microbiota richness are found in Chinese patients with IBS-D, which may be used to diagnose dysbiosis in these patients.
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Bacillus licheniformis prevents and reduces anxiety-like and depression-like behaviours.
As common mental disorders, depression and anxiety impact people all around the world. Recent studies have found that the gut microbiome plays an important role in mental health. It is becoming possible to treat mental disorders by regulating the composition of the gut microbiota. Bacillus licheniformis is a probiotic used to treat gut diseases through balancing the gut microbiome during lasting years. Considering the role of gut microbiota in the gut-brain axis, this study used chronic unpredictable mild stress (CUMS) model rats to explore whether Bacillus licheniformis can prevent and treat depression and anxiety. We found that B. licheniformis reduced the depressive-like and anxiety-like behaviours of the rats during the CUMS process. Meanwhile, B. licheniformis changed the gut microbiota composition; increased the short chain fatty acids (SCFAs) in the colon, decreased kynurenine, norepinephrine, and glutamate levels; and increased the tryptophan, dopamine, epinephrine, and γ-aminobutyric acid (GABA) in the brain. After correlation analysis, we found Parabacteroides, Anaerostipes, Ruminococcus-2, and Blautia showed significant correlation with neurotransmitters and SCFAs, indicating the gut microbiome plays an important role in B. licheniformis reducing depressive-like behaviours. Therefore, this study suggested B. licheniformis may prevent depressive-like and anxiety-like behaviours while regulating the gut microbiota composition and increasing the SCFA levels in the colon to alter the levels of the neurotransmitters in the brain. KEY POINTS: • B. licheniformis reduced depressive-like and anxiety-like behaviours induced by the chronic unpredictable mild stress. • GABA levels in the brain are assonated with B. licheniformis regulating depressive-like and anxiety-like behaviours. • Gut microbiota composition alteration followed by metabolic changes may play a role in the GABA levels increase.
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Gut microbiota profiling reflects the renal dysfunction and psychological distress in patients with diabetic kidney disease.
BACKGROUND: The gut microbiota plays a pivotal role in the development of diabetes and kidney disease. However, it is not clear how the intestinal microecological imbalance is involved in the context of diabetic kidney disease (DKD), the leading cause of renal failure. OBJECTIVES: To elucidate the gut microbial signatures associated with DKD progression towards end-stage renal disease (ESRD) and explore whether they could reflect renal dysfunction and psychological distress. METHODS: A cross-sectional study was conducted to explore the gut microbial signatures of 29 DKD non-ESRD patients and 19 DKD ESRD patients compared to 20 healthy controls. Differential analysis was performed to detect distinct gut microbial alterations in diversities and taxon abundance of DKD with and without ESRD. Renal dysfunction was estimated by urea, creatinine, and estimated glomerular filtration rate. Psychological distress was assessed using the Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale. RESULTS: Alpha diversity indexes were reduced in DKD patients, particularly those with ESRD. Beta diversity analysis revealed that the gut microbial compositions of DKD patients were different with healthy individuals whereas similar compositions were observed in DKD patients. Taxon differential analysis showed that when compared with the controls, DKD patients exhibit distinct microbial profiles including reduced abundances of butyrate-produced, anti-inflammatory bacteria Faecalibacterium, Lachnospira, Roseburia Lachnoclostridium, and increased abundances of pro-inflammatory bacteria Collinsella, Streptococcus etc. These distinctive genera presented consistent associations with renal dysfunction, as well as psychological distress, especially in DKD patients. CONCLUSIONS: DKD patients, especially those who have progressed to ESRD, exhibit unique characteristics in their gut microbiota that are associated with both renal dysfunction and psychological distress. The gut microbiota may be a significant factor in the deterioration of DKD and its eventual progression to ESRD.
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ESRRA (estrogen related receptor alpha) is a critical regulator of intestinal homeostasis through activation of autophagic flux via gut microbiota.
The orphan nuclear receptor ESRRA (estrogen related receptor alpha) is critical in mitochondrial biogenesis and macroautophagy/autophagy function; however, the roles of ESRRA in intestinal function remain uncharacterized. Herein we identified that ESRRA acts as a key regulator of intestinal homeostasis by amelioration of colonic inflammation through activation of autophagic flux and control of host gut microbiota. Esrra-deficient mice presented with increased susceptibility to dextran sodium sulfate (DSS)-induced colitis with upregulation of intestinal inflammation. In addition, esrra-null mice had depressed AMP-activated protein kinase phosphorylation (AMPK), lower levels of TFEB (transcription factor EB), and accumulation of SQSTM1/p62 (sequestosome 1) with defective mitochondria in intestinal tissues. Esrra-deficient mice showed distinct gut microbiota composition and significantly higher microbial diversity than wild-type (WT) mice. Cohousing or fecal microbiota transplantation from WT mice to Esrra-deficient mice ameliorated DSS-induced colitis severity. Importantly, patients with ulcerative colitis (UC) had significantly decreased ESRRA expression in intestinal mucosal tissues that correlated with disease activity, suggesting clinical relevance of ESRRA in UC. Taken together, our results show that ESRRA contributes to intestinal homeostasis through autophagy activation and gut microbiota control to protect the host from detrimental inflammation and dysfunctional mitochondria.Abbreviations: ABX, antibotics; AMPK, AMP-activated protein kinase; ATP5A1, ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1; BECN1, beclin1, autophagy related, CCL, C-C motif chemokine ligand; CD, Crohn disease; CLDN, claudin; COX4I1, cytochrome c oxidase subunit 4I1; cKO, conditional knockout; cWT, conditional wild-type; CXCL, C-X-C motif chemokine ligand; DAI, disease activity index; DSS, dextran sodium sulfate; EGFP, enhanced green fluorescent protein; ESRR, estrogen related receptor; ESRRA, estrogen related receptor alpha; Esrra+/+, Esrra wild type; esrra-/-, esrra homozygous knockout; FMT, fecal microbiota transplantation; GABARAP, gamma-aminobutyric acid receptor associated protein; GSEA, gene set enrichment analysis; IBD, inflammatory bowel disease; IL, interleukin; KO, knockout; LAMP1, lysosomal-associated membrane protein 1; LCN2, lipocalin 2; LEfSe, linear discriminant analysis (LDA) effect size; LPS, lipopolysachharide; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; NDUFAB1, NADH: ubiquinone oxidoreductase subunit AB1; OCLN, occludin; OUT, operational taxonomic unit; OXPHOS, oxidative phosphorylation; PCoA, principal coordinate analysis; PPARGC1A, PPARG coactiva- tor 1 alpha; PRKAA, 5'-AMP-activated protein kinase catalytic subunit alpha; PTGS2/COX2, prostaglandin-endoperoxide synthase 2; RAB7, member RAS oncogene family; SDHB, succinate dehydrogenase complex, subunit B, iron sulfur (Ip); SQSTM1/p62, sequestosome 1; S100A9, S100 calcium binding protein A9 (calgranulin B); TCA, tricarboxylic acid; TFEB, transcription factor EB; TNF, tumor necrosis factor; UC, ulcerative colitis; UCP2, uncoupling protein 2 (mitochondrial, proton carrier); UQCRC1, ubiquinol-cytochrome c reductase core protein 1; UVRAG, UV radiation resistance associated gene; Vil1, villin; VPS11, VPS11, CORVET/HOPS core sub-unit; WT, wild type.
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Fecal transplant prevents gut dysbiosis and anxiety-like behaviour after spinal cord injury in rats.
Secondary manifestations of spinal cord injury beyond motor and sensory dysfunction can negatively affect a person's quality of life. Spinal cord injury is associated with an increased incidence of depression and anxiety; however, the mechanisms of this relationship are currently not well understood. Human and animal studies suggest that changes in the composition of the intestinal microbiota (dysbiosis) are associated with mood disorders. The objective of the current study is to establish a model of anxiety following a cervical contusion spinal cord injury in rats and to determine whether the microbiota play a role in the observed behavioural changes. We found that spinal cord injury caused dysbiosis and increased symptoms of anxiety-like behaviour. Treatment with a fecal transplant prevented both spinal cord injury-induced dysbiosis as well as the development of anxiety-like behaviour. These results indicate that an incomplete unilateral cervical spinal cord injury can cause affective disorders and intestinal dysbiosis, and that both can be prevented by treatment with fecal transplant therapy.
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Systematic Review of Gut Microbiota and Major Depression.
Background: Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder (MDD). Bacterial transplantation from MDD patients to rodents produces depression-like behaviors. In humans, case-control studies have examined the gut microbiome in healthy and affected individuals. We systematically reviewed existing studies comparing gut microbial composition in MDD and healthy volunteers. Methods: A PubMed literature search combined the terms "depression," "depressive disorder," "stool," "fecal," "gut," and "microbiome" to identify human case-control studies that investigated relationships between MDD and microbiota quantified from stool. We evaluated the resulting studies, focusing on bacterial taxa that were different between MDD and healthy controls. Results: Six eligible studies were found in which 50 taxa exhibited differences (p < 0.05) between patients with MDD and controls. Patient characteristics and methodologies varied widely between studies. Five phyla-Bacteroidetes, Firmicutes, Actinobacteria, Fusobacteria, and Protobacteria-were represented; however, divergent results occurred across studies for all phyla. The largest number of differentiating taxa were within phylum Firmicutes, in which nine families and 12 genera differentiated the diagnostic groups. The majority of these families and genera were found to be statistically different between the two groups in two identified studies. Family Lachnospiraceae differentiated the diagnostic groups in four studies (with an even split in directionality). Across all five phyla, nine genera were higher in MDD (Anaerostipes, Blautia, Clostridium, Klebsiella, Lachnospiraceae incertae sedis, Parabacteroides, Parasutterella, Phascolarctobacterium, and Streptococcus), six were lower (Bifidobacterium, Dialister, Escherichia/Shigella, Faecalibacterium, and Ruminococcus), and six were divergent (Alistipes, Bacteroides, Megamonas, Oscillibacter, Prevotella, and Roseburia). We highlight mechanisms and products of bacterial metabolism as they may relate to the etiology of depression. Conclusions: No consensus has emerged from existing human studies of depression and gut microbiome concerning which bacterial taxa are most relevant to depression. This may in part be due to differences in study design. Given that bacterial functions are conserved across taxonomic groups, we propose that studying microbial functioning may be more productive than a purely taxonomic approach to understanding the gut microbiome in depression.
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Low fermentable, oligo-, di-, mono-saccharides and polyol diet in the treatment of irritable bowel syndrome: A systematic review and meta-analysis.
OBJECTIVES: The aim of this review was to systematically assess and meta-analyze the effects of a low fermentable, oligo-, di-, mono-saccharides and polyol (FODMAP) diet (LFD) on the severity of symptoms, quality of life, and safety in patients with irritable bowel syndrome (IBS). METHODS: The MEDLINE/PubMed, Scopus, and Cochrane Library databases were screened through January 19, 2016. Randomized controlled trials (RCTs) that compared LFD to other diets were included if they assessed symptoms of IBS or abdominal pain in patients with IBS. Safety, quality of life, anxiety, depression, and effect on gut microbiota were defined as secondary outcomes. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated. RESULTS: Nine RCTs with a total of 596 subjects were included. Three RCTs compared LFD with a habitual diet, two RCTs provided all meals and compared LFD with a western diet, one RCT each compared LFD with a diet high in FODMAPs or a sham diet, and two RCTs compared with other diet recommendations for IBS. A meta-analysis revealed significant group differences for LFD compared with other diets with regard to gastrointestinal symptoms (SMD = -0.62; 95% CI = -0.93 to -0.31; P = 0.0001), abdominal pain (SMD = -0.50; 95% CI = -0.77 to -0.22; P = 0.008), and health-related quality of life (SMD = 0.36; 95% CI = 0.10-0.62; P = 0.007). Three studies reported a significant reduction in luminal bifidobacteria after LFD. Adverse events were assessed in three RCTs only and no intervention-related adverse events were reported. CONCLUSIONS: This meta-analysis found evidence of the short-term efficacy and safety of LFD in patients with IBS. However, only a preliminary recommendation for LFD can be made until long-term effects are investigated.
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The impact of DASH diet and concurrent training on cardiometabolic risk factors and gut microbiota in individuals with ischemic heart disease: a study protocol for a randomized controlled trial.
BACKGROUND: Ischemic heart disease (IHD) has a substantial burden on individuals and health system infrastructure worldwide. Meanwhile, mounting evidence has declared remarkable contrasts in gut microbiota between individuals with IHD and healthy counterparts. The Dietary Approaches to Stop Hypertension (DASH) might be one of the most reliable strategies to manage cardiometabolic risk factors. Nonetheless, no experiment has tested the impact of a DASH diet and exercise on gut microbiota composition in IHD individuals. Hence, we aim to explore the effects of a DASH diet and concurrent exercise on gut microbiota, oxidized LDL, and cardiometabolic risk factors among men. METHODS: In total, 48 men aged 40-70 years with IHD will be recruited in this parallel randomized, controlled, 2 × 2 factorial clinical trial. These patients will be randomly assigned to the following four intervention groups: DASH diet (D), concurrent exercise (E), concurrent DASH diet and exercise (DE), and control (usual care) (C) for 8 weeks. At baseline and the end of the study, stool samples and serum levels will be gathered to detect gut microbiota (Firmicutes, Bacteroidetes, Bifidobacteria, clostridium, Faecalibacterium prausnitzi, Bacteroidetes, and Akkermansia muciniphila) and cardiometabolic risk factors, as well as anthropometric measures, blood pressure, quality of life, 6-min walking test, and Beck Depression Inventory (BDI). DISCUSSION: Based on our information, the present study is the primary randomized controlled trial testing the impacts of short-term concurrent training and DASH diet on intestinal bacteria diversity and several cardiometabolic risk factors in men with IHD. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (www.irct.ir, IRCT20181205041859N1). Registered on 29 September 2024.
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Transport stress alters serum biochemistry and gut microbiota in Tibetan sheep (ovis aries): a 30-day recovery assessment.
BACKGROUND: Transport stress poses a major challenge to the livestock industry. Studies have shown that transportation stress can cause depression, elevated body temperature and dysbiosis of intestinal microbiota in meat goats, and in severe cases, even lead to death of the animals, which in turn affects the economic efficiency of the farming industry. However, the changes in blood biochemical indicators and flora of Tibetan sheep throughout the receiving period after long-distance transport remain unclear. METHODS: In this study, six 7-month-old Tibetan sheep with similar body weights were selected for a 30-d transport trial, and blood and faecal samples were collected for blood biochemical indices and 16 S microbiome sequencing before transport (BT), and on day 1 (AT 1), day 16 (AT 16), and day 30 (AT 30) after the end of the transport, respectively. RESULT: And a number of blood biochemical indices (creatine kinase (CK), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate aminotransferase (AST), cortisol (COR), and adrenocorticotropic hormone (ACTH)) were significantly elevated (P < 0.05). Combined analysis of physiological and biochemical indices with 16 S rDNA sequencing showed that Turicibacter, Romboutsia and Clostridium_sensu_stricto_1 were positively correlated with LDH, ALP, CK, AST, and ACTH, while Prevotellaceae_UCG_004 was negatively correlated. Furthermore, the observed recovery trends in vital signs after AT 16 suggest that Tibetan sheep may be able to adapt to the new environment within one month post-transport. The present study illustrated the effects of transport without measures on the vital signs, serum biochemical indicators and faecal microorganisms of Tibetan sheep throughout the receiving period, which is of great significance in guiding the transport of Tibetan sheep and solving the damage caused by transport stress on the economic benefits of the farming industry.