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Gut Microbes 2024Diarrhea-predominant irritable bowel syndrome (IBS-D), associated with increased intestinal permeability, inflammation, and small intestinal bacterial overgrowth, can be...
Diarrhea-predominant irritable bowel syndrome (IBS-D), associated with increased intestinal permeability, inflammation, and small intestinal bacterial overgrowth, can be triggered by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by gastroenteritis-causing pathogens and may underlie IBS-D development, through molecular mimicry with vinculin. Here, we examine the effects of exposure to CdtB alone on gut microbiome composition, host intestinal gene expression, and IBS-D-like phenotypes in a rat model. CdtB-inoculated rats exhibited increased anti-CdtB levels, which correlated with increased stool wet weights, pro-inflammatory cytokines (TNFα, IL2) and predicted microbial metabolic pathways including inflammatory responses, TNF responses, and diarrhea. Three distinct ileal microbiome profiles (microtypes) were identified in CdtB-inoculated rats. The first microtype (most like controls) had altered relative abundance (RA) of genera and . The second had lower microbial diversity, higher RA, higher absolute abundance, and altered host ileal tissue expression of immune-response and TNF-response genes compared to controls. The third microtype had higher microbial diversity, higher RA of hydrogen sulfide (HS)-producer , and increased expression of HS-associated pain/serotonin response genes. All CdtB-inoculated rats exhibited decreased ileal expression of cell junction component mRNAs, including vinculin-associated proteins. Significantly, cluster-specific microRNA-mRNA interactions controlling intestinal permeability, visceral hypersensitivity/pain, and gastrointestinal motility genes, including several previously associated with IBS were seen. These findings demonstrate that exposure to CdtB toxin alone results in IBS-like phenotypes including inflammation and diarrhea-like stool, decreased expression of intestinal barrier components, and altered ileal microtypes that influenced changes in microRNA-modulated gene expression and predicted metabolic pathways consistent with specific IBS-D symptoms.
Topics: Rats; Animals; Irritable Bowel Syndrome; Rodentia; Vinculin; Escherichia coli; Gastrointestinal Microbiome; Diarrhea; Inflammation; Gastroenteritis; Gene Expression; Pain
PubMed: 38108386
DOI: 10.1080/19490976.2023.2293170 -
Heliyon Dec 2023Dioctyl phthalate, commonly known as bis(2-ethylhexyl) phthalate (DEHP), is a widely used plasticizer in various industries and has been shown to directly or indirectly...
Dioctyl phthalate, commonly known as bis(2-ethylhexyl) phthalate (DEHP), is a widely used plasticizer in various industries and has been shown to directly or indirectly impact human health. However, there is a lack of comprehensive studies evaluating the potential health risks associated with DEHP accumulation in different organs across various age groups. This study aimed to assess the effects of low (50 mg/kg·bw) and high (500 mg/kg·bw) doses of DEHP on five different organs in mice at young (4-week-old) and aged (76-week-old) life stages. Our findings revealed that both low and high doses of DEHP exposure led to significant dose-dependent inflammation in the liver, spleen, and kidney. Furthermore, regardless of age, DEHP exposure resulted in elevated activity of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the liver, as well as increased levels of creatinine (Cr) and urea in the kidney. Moreover, analysis of the fecal microbiota using 16S rRNA sequencing demonstrated that DEHP exposure disrupted the homeostasis of the gut microbiota, characterized by an increased abundance of pathogenic bacteria such as and , and a decreased abundance of beneficial bacteria like . This study provides compelling evidence that DEHP at different concentrations can induce damage to multiple organs and disrupt gut microbiota composition. These findings lay the groundwork for further investigations into DEHP toxicity in various human organs, contributing to a better understanding of the potential health risks associated with DEHP exposure.
PubMed: 38107267
DOI: 10.1016/j.heliyon.2023.e22677 -
Frontiers in Microbiology 2023The intricate interplay between gut microbiota and hyperuricemia remains a subject of growing interest. However, existing studies only provided snapshots of the gut...
INTRODUCTION
The intricate interplay between gut microbiota and hyperuricemia remains a subject of growing interest. However, existing studies only provided snapshots of the gut microbiome at single time points, the temporal dynamics of gut microbiota alterations during hyperuricemia progression and the intricate interplay between the gut barrier and microbiota remain underexplored. Our investigation revealed compelling insights into the dynamic changes in both gut microbiota and intestinal barrier function throughout the course of hyperuricemia.
METHODS
The hyperuricemia mice (HY) were given intragastric administration of adenine and potassium oxalate. Gut microbiota was analyzed by 16S rRNA sequencing at 3, 7, 14, and 21 days after the start of the modeling process. Intestinal permeability as well as LPS, TNF-α, and IL-1β levels were measured at 3, 7, 14, and 21 days.
RESULTS
We discovered that shifts in microbial community composition occur prior to the onset of hyperuricemia, key bacterial , , and exhibited reduced levels, potentially fueling microbial dysbiosis as the disease progresses. During the course of hyperuricemia, the dynamic fluctuations in both uric acid levels and intestinal barrier function was accompanied with the depletion of key beneficial bacteria, including , , , , and , and coincided with an increase in pathogenic bacteria such as and . This microbial community shift likely contributed to elevated lipopolysaccharide (LPS) and pro-inflammatory cytokine levels, ultimately promoting metabolic inflammation. The decline of and was inversely related to uric acid levels, Conversely, key families , , genera exhibited positive correlations with uric acid levels. and demonstrating negative correlations, while LPS-containing microbiota such as and exhibited positive correlations with intestinal permeability.
CONCLUSION
In summary, this study offers a dynamic perspective on the complex interplay between gut microbiota, uric acid levels, and intestinal barrier function during hyperuricemia progression. Our study suggested that Ruminiclostridium, Bacteroides, Akkermansiaceae, Bilophila, Burkholderiaceae and Parasutterella were the key bacteria that play vital rols in the progress of hyperuricemia and compromised intestinal barrier, which provide a potential avenue for therapeutic interventions in hyperuricemia.
PubMed: 38088975
DOI: 10.3389/fmicb.2023.1287468 -
Frontiers in Microbiology 2023The association between gut microbiota and leukemia has been established, but the causal relationship between the two remains unclear.
BACKGROUND
The association between gut microbiota and leukemia has been established, but the causal relationship between the two remains unclear.
METHODS
A bidirectional two-sample Mendelian randomization (MR) was used to analyze the causal relationship between gut microbiota and leukemia. Microbiome data ( = 14,306) and leukemia ( = 1,145) data were both sourced from European populations. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on several criteria. We employed various MR methods, such as the inverse variance weighted (IVW) method, to evaluate the causal effect between exposure and outcomes and conducted sensitivity analyses to validate the heterogeneity and pleiotropy of the instrumental variables.
RESULTS
5,742 qualified instrumental variables were included. In the primary MR results, a total of 10 gut microbial taxa were associated with leukemia risk. Genus Blautia and genus Lactococcus are risk factors for acute lymphoblastic leukemia [genus Blautia odds ratio (OR): 1.643, 95% confidence interval (CI): 1.592 ~ 1.695, Adjusted < 0.001; genus Lactococcus OR: 2.152, 95% CI: 1.447 ~ 3.199, Adjusted = 0.011]. Genus Rikenellaceae RC9 gut group, genus Anaerostipes, genus Slackia, and genus Lachnospiraceae ND3007 group are risk factors for acute myeloid leukemia [genus Rikenellaceae RC9 gut group OR: 1.964, 95% CI: 1.573 ~ 2.453, Adjusted < 0.001; genus Anaerostipes OR: 2.515, 95% CI: 1.503 ~ 4.209, Adjusted = 0.017; genus Slackia OR: 2.553, 95% CI: 1.481 ~ 4.401, Adjusted = 0.022; genus Lachnospiraceae ND3007 group OR: 3.417, 95% CI: 1.960 ~ 5.959, Adjusted = 0.001]. Genus Ruminococcaceae UCG011 and genus Ruminococcaceae UCG014 were risk factors for chronic myeloid leukemia (genus Ruminococcaceae UCG011 OR: 2.010, 95% CI: 1.363 ~ 2.963, Adjusted = 0.044; genus Ruminococcaceae UCG014 OR: 3.101, 95% CI: 1.626 ~ 5.915, Adjusted = 0.044). Genus Slackia was a protective factor for acute lymphoblastic leukemia (genus Slackia OR: 0.166, 95% CI: 0.062 ~ 0.443, Adjusted = 0.017). Family Acidaminococcaceae was a protective factor for acute myeloid leukemia (family Acidaminococcaceae OR: 0.208, 95% CI: 0.120 ~ 0.361, Adjusted 0.001). Genus Desulfovibrio was a protective factor for chronic lymphoblastic leukemia (genus Desulfovibrio OR: 0.581, 95% CI: 0.440 ~ 0.768, Adjusted = 0.020). Sensitivity analysis revealed no heterogeneity or pleiotropy between SNPs.
CONCLUSION
This study revealed the causal relationship between the gut microbiota and leukemia, and identified potential pathogenic bacteria and probiotic taxa associated with the onset of leukemia. This research may aid in the early detection of various types of leukemia and offer a new direction for the prevention and treatment of leukemia.
PubMed: 38075916
DOI: 10.3389/fmicb.2023.1293333 -
Nutrients Dec 2023The edible fungus (ADe) is commonly employed in traditional medicine for intestinal disorders; however, its inhibitory effect on colitis-associated colorectal cancer...
BACKGROUND
The edible fungus (ADe) is commonly employed in traditional medicine for intestinal disorders; however, its inhibitory effect on colitis-associated colorectal cancer (CAC) and the underlying mechanisms remain unexplored. (2) Methods: The inhibitory effect of ADe on CAC was investigated using a mouse model induced by azoxymethane/dextran sulfate sodium.
RESULTS
ADe effectively suppressed the growth and number of intestinal tumors in mice. Intestinal microbiota analyses revealed that ADe treatment increased and while it decreased , , , and . ADe regulated the levels of 2'-deoxyridine, creatinine, 1-palmitoyl lysophosphatidylcholine, and choline in serum. Furthermore, the levels of these metabolites were associated with the abundance of and . ADe up-regulated the free fatty acid receptor 2 and β-Arrestin 2, inhibited the nuclear factor kappa B (NF-κB) pathway, and significantly attenuated the levels of inflammatory cytokines, thereby mitigating the inflammatory in CAC mice.
CONCLUSIONS
The protective effect of ADe in CAC mice is associated with the regulation of intestinal microbiota, which leads to the inhibition of NF-kB pathway and regulation of inflammation.
Topics: Animals; Mice; Colitis; Auricularia; Colitis-Associated Neoplasms; Gastrointestinal Microbiome; Inflammation; NF-kappa B; Dextran Sulfate; Mice, Inbred C57BL; Disease Models, Animal; Colon
PubMed: 38068869
DOI: 10.3390/nu15235011 -
Digestive Diseases and Sciences Feb 2024We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (HS)-producing...
BACKGROUND
We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (HS)-producing Fusobacterium and Desulfovibrio species, and constipation-predominant IBS (IBS-C) subjects have higher RA of methanogen Methanobrevibacter smithii.
AIMS
In this study, we investigate the effects of increased methanogens or HS producers on stool phenotypes in rat models.
METHODS
Adult Sprague-Dawley rats were fed high-fat diet (HFD) for 60 days to increase M. smithii levels, then gavaged for 10 days with water (controls) or methanogenesis inhibitors. To increase HS producers, rats were gavaged with F. varium or D. piger. Stool consistency (stool wet weight (SWW)) and gas production were measured. 16S rRNA gene sequencing was performed on stool samples.
RESULTS
In HFD diet-fed rats (N = 30), stool M. smithii levels were increased (P < 0.001) after 52 days, correlating with significantly decreased SWW (P < 0.0001) at 59 days (R = - 0.38, P = 0.037). Small bowel M. smithii levels decreased significantly in lovastatin lactone-treated rats (P < 0.0006), and SWW increased (normalized) in lovastatin hydroxyacid-treated rats (P = 0.0246), vs. controls (N = 10/group). SWW increased significantly in D. piger-gavaged rats (N = 16) on day 10 (P < 0.0001), and in F. varium-gavaged rats (N = 16) at all timepoints, vs. controls, with increased stool HS production. 16S sequencing revealed stool microbiota alterations in rats gavaged with HS producers, with higher relative abundance (RA) of other HS producers, particularly Lachnospiraceae and Bilophila in F. varium-gavaged rats, and Sutterella in D. piger-gavaged rats.
CONCLUSIONS
These findings suggest that increased M. smithii levels result in a constipation-like phenotype in a rat model that is partly reversible with methanogenesis inhibitors, whereas gavage with HS producers D. piger or F. varium results in increased colonization with other HS producers and diarrhea-like phenotypes. This supports roles for the increased RA of methanogens and HS producers identified in IBS-C and IBS-D subjects, respectively, in contributing to stool phenotypes.
Topics: Humans; Adult; Rats; Animals; Irritable Bowel Syndrome; Hydrogen Sulfide; Methane; RNA, Ribosomal, 16S; Rats, Sprague-Dawley; Constipation; Diarrhea; Models, Animal; Lovastatin
PubMed: 38060167
DOI: 10.1007/s10620-023-08197-5 -
Revista Brasileira de Parasitologia... 2023In vitro excystation of cysts of microscopically identified Chilomastix mesnili and Retortamonas sp. isolated from Japanese macaques and Retortamonas sp. isolated from...
In vitro excystation of cysts of microscopically identified Chilomastix mesnili and Retortamonas sp. isolated from Japanese macaques and Retortamonas sp. isolated from small Indian mongooses could be induced using an established protocol for Giardia intestinalis and subsequently by culturing with H2S-rich Robinson's medium supplemented with Desulfovibrio desulfuricans. Excystation usually began 2 h after incubation in Robinson's medium. DNA was isolated from excysted flagellates after 4 h of incubation or from cultured excysted flagellates. Phylogenetic analysis based on their 18S rRNA genes revealed that two isolates of C. mesnili from Japanese macaques belonged to the same cluster as a C. mesnili isolate from humans, whereas a mammalian Retortamonas sp. isolate from a small Indian mongoose belonged to the same cluster as that of an amphibian Retortamonas spp. isolate from a 'poison arrow frog' [sequence identity to AF439347 (94.9%)]. These results suggest that the sequence homology of the 18S rRNA gene of the two C. mesnili isolates from Japanese macaques was similar to that of humans, in addition to the morphological similarity, and Retortamonas sp. infection of the amphibian type in the small Indian mongoose highlighted the possibility of the effect of host feeding habitats.
Topics: Humans; Animals; Phylogeny; Retortamonadidae; Herpestidae; Macaca fuscata; Parasites; RNA, Ribosomal, 18S
PubMed: 38055438
DOI: 10.1590/S1984-29612023070 -
Frontiers in Cellular and Infection... 2023There are several clinical and molecular predictors of responses to antidepressant therapy. However, these markers are either too subjective or complex for clinical use....
BACKGROUND
There are several clinical and molecular predictors of responses to antidepressant therapy. However, these markers are either too subjective or complex for clinical use. The gut microbiota could provide an easily accessible set of biomarkers to predict therapeutic efficacy, but its value in predicting therapy responses to acupuncture in patients with depression is unknown. Here we analyzed the predictive value of the gut microbiota in patients with postpartum depressive disorder (PPD) treated with acupuncture.
METHODS
Seventy-nine PPD patients were enrolled: 55 were treated with acupuncture and 24 did not received any treatment. The 17-item Hamilton depression rating scale (HAMD-17) was used to assess patients at baseline and after eight weeks. Patients receiving acupuncture treatment were divided into an acupuncture-responsive group or non-responsive group according to HAMD-17 scores changes. Baseline fecal samples were obtained from the patients receiving acupuncture and were analyzed by high-throughput 16S ribosomal RNA sequencing to characterize the gut microbiome.
RESULTS
47.27% patients responded to acupuncture treatment and 12.5% patients with no treatment recovered after 8-week follow-up. There was no significant difference in α-diversity between responders and non-responders. The β-diversity of non-responders was significantly higher than responders. and spp. were significantly enriched in acupuncture responders, and these organisms had an area under the curve of 0.76 and 0.66 for predicting responder patients, respectively.
CONCLUSIONS
and are may be useful predictive biomarkers to predict PPD patients likely to respond to acupuncture. Larger studies and validation in independent cohorts are now needed to validate our findings.
Topics: Female; Humans; Treatment Outcome; Acupuncture Therapy; Microbiota; Depressive Disorder; Biomarkers; Postpartum Period
PubMed: 38053532
DOI: 10.3389/fcimb.2023.1228940 -
Revista Espanola de Quimioterapia :... Feb 2024
Topics: Humans; Abscess; Desulfovibrio desulfuricans; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Anti-Bacterial Agents; Actinobacteria
PubMed: 38050695
DOI: 10.37201/req/081.2023 -
BioRxiv : the Preprint Server For... Nov 2023Biofilms of the sulfate reducing bacterium (SRB) Hildenborough (DvH) can facilitate metal corrosion in various industrial and environmental settings leading to...
Biofilms of the sulfate reducing bacterium (SRB) Hildenborough (DvH) can facilitate metal corrosion in various industrial and environmental settings leading to substantial economic losses; however, the mechanisms of biofilm formation by DvH are not yet well-understood. Evidence suggests that a large adhesin, DvhA, may be contributing to biofilm formation in DvH. The gene and its neighbors encode proteins that resemble the Lap system, which regulates biofilm formation by , including a LapG-like protease DvhG and effector protein DvhD, which has key differences from the previously described LapD. By expressing the Lap-like adhesion components of DvH in , our data support the model that the N-terminal fragment of the large adhesin DvhA serves as an adhesin "retention module" and is the target of the DvhG/DvhD regulatory module, thereby controlling cell-surface location of the adhesin. By heterologously expressing the DvhG/DvhD-like proteins in a background lacking native regulation (ΔΔ) we also show that cell surface regulation of the adhesin is dependent upon the intracellular levels of c-di-GMP. This study provides insight into the key players responsible for biofilm formation by DvH, thereby expanding our understanding of Lap-like systems.
PubMed: 38045380
DOI: 10.1101/2023.11.22.568322