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1.
Gut Microbes ; 16(1): 2363020, 2024.
Article in English | MEDLINE | ID: mdl-38841892

ABSTRACT

CD4+ T cells play a critical role in regulating autoimmune diseases, and intestinal microbial metabolites control various immune responses. Granzyme B (GzmB)-producing CD4+ T cells have been recently reported to participate in the pathogenesis of autoimmune diseases. Here, we found that GzmbB-deficient CD4+ T cells induced more severe colitis in Rag1-/- mice than wild-type (WT) CD4+ T cells. Germ-free (GF) mice exhibited a lower expression of GzmB in intestinal CD4+ T cells compared to specific pathogen-free (SPF) mice. Intestinal microbial metabolite butyrate increased GzmB expression in CD4+ T cells, especially in IL-10-producing Th1 cells, through HDAC inhibition and GPR43, but not GPR41 and GPR109a. Butyrate-treated GzmB-deficient CD4+ T cells demonstrated more severe colitis compared to butyrate-treated WT CD4+ T cells in the T cell transfer model. Butyrate altered intestinal microbiota composition, but altered microbiota did not mediate butyrate induction of intestinal CD4+ T cell expression of GzmB in mice. Blimp1 was involved in the butyrate induction of GzmB in IL-10-producing Th1 cells. Glucose metabolism, including glycolysis and pyruvate oxidation, mediated butyrate induction of GzmB in Th1 cells. In addition, we found that IKZF3 and NR2F6 regulated GzmB expression induced by butyrate. Together, our studies underscored the critical role of GzmB in mediating gut bacterial metabolite butyrate regulation of T cell tolerance at the mucosal surface.


Subject(s)
Butyrates , Colitis , Gastrointestinal Microbiome , Granzymes , Interleukin-10 , Mice, Inbred C57BL , Th1 Cells , Animals , Interleukin-10/metabolism , Interleukin-10/genetics , Interleukin-10/immunology , Th1 Cells/immunology , Mice , Gastrointestinal Microbiome/drug effects , Butyrates/metabolism , Butyrates/pharmacology , Granzymes/metabolism , Colitis/immunology , Colitis/microbiology , Colitis/metabolism , Mice, Knockout , Positive Regulatory Domain I-Binding Factor 1/metabolism , Positive Regulatory Domain I-Binding Factor 1/genetics , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Immune Tolerance , Homeodomain Proteins
2.
Appl Microbiol Biotechnol ; 108(1): 372, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874789

ABSTRACT

Methanol is a promising feedstock for the bio-based economy as it can be derived from organic waste streams or produced electrochemically from CO2. Acetate production from CO2 in microbial electrosynthesis (MES) has been widely studied, while more valuable compounds such as butyrate are currently attracting attention. In this study, methanol was used as a co-substrate with CO2 to enhance butyrate production in MES. Feeding with CO2 and methanol resulted in the highest butyrate production rates and titres of 0.36 ± 0.01 g L-1 d-1 and 8.6 ± 0.2 g L-1, respectively, outperforming reactors with only CO2 feeding (0.20 ± 0.03 g L-1 d-1 and 5.2 ± 0.1 g L-1, respectively). Methanol acted as electron donor and as carbon source, both of which contributed ca. 50% of the carbon in the products. Eubacterium was the dominant genus with 52.6 ± 2.5% relative abundance. Thus, we demonstrate attractive route for the use of the C1 substrates, CO2 and methanol, to produce mainly butyrate. KEY POINTS: • Butyrate was the main product from methanol and CO2 in MES • Methanol acted as both carbon and electron source in MES • Eubacterium dominating microbial culture was enriched in MES.


Subject(s)
Butyrates , Carbon Dioxide , Methanol , Methanol/metabolism , Carbon Dioxide/metabolism , Butyrates/metabolism , Bioreactors/microbiology , Carbon/metabolism , Acetates/metabolism
3.
Anim Sci J ; 95(1): e13954, 2024.
Article in English | MEDLINE | ID: mdl-38797605

ABSTRACT

This study investigated the physiological characteristics and carcass performance associated with residual methane emissions (RME), and the effects of bull differences on CH4-related traits in Japanese Black cattle. Enteric methane (CH4) emissions from 156 Japanese Black cattle (111 heifers and 45 steers) were measured during early fattening using the sniffer method. Various physiological parameters were investigated to clarify the physiological traits between the high, middle, and low RME groups. CH4-related traits were examined to determine whether bull differences affected progeny CH4 emissions. Ruminal butyrate and NH3 concentrations were significantly higher in the high-RME group than in the low-RME group, whereas the propionate content was significantly higher in the low-RME group. Blood urea nitrogen, ß-hydroxybutyric acid, and insulin concentrations were significantly higher, and blood amino acids were lower in the high-RME group than in the other groups. No significant differences were observed in the carcass traits and beef fat composition between RME groups. CH4-related traits were significantly different among bull herds. Our results show that CH4-related traits are heritable, wherein bull differences affect progeny CH4 production capability, and that the above-mentioned rumen fermentations and blood metabolites could be used to evaluate enteric methanogenesis in Japanese Black cattle.


Subject(s)
Butyrates , Methane , Rumen , Animals , Methane/metabolism , Cattle/metabolism , Cattle/physiology , Male , Rumen/metabolism , Female , Butyrates/metabolism , Ammonia/metabolism , Ammonia/blood , Ammonia/analysis , Fermentation , 3-Hydroxybutyric Acid/blood , Propionates/metabolism , Blood Urea Nitrogen , Insulin/blood , Insulin/metabolism
4.
Anim Sci J ; 95(1): e13955, 2024.
Article in English | MEDLINE | ID: mdl-38769748

ABSTRACT

This study was conducted to assess the effects of fermented rice bran (FRB) with Ligilactobacillus equi on ruminal fermentation using an in vitro system. Oat hay, corn starch, and wheat bran were used as substrate for control. Ten percent of wheat bran was replaced with rice bran (RB), rice bran fermented with distilled water, and rice bran fermented with L. equi for T1, T2, and T3, respectively. The experimental diets were mixed with buffered rumen fluid from wethers under nitrogen gas and incubated for 24 h at 39°C. The fermentation profile and microbial population were analyzed after the incubations. The results revealed that the RB and FRB (with or without L. equi) significantly reduced the gas, methane (CH4), and CH4 per dry matter digested (p < 0.001). Total short-chain fatty acid was also reduced in T1 and T2 in comparison with the control (p < 0.001). Propionate proportion was increased while butyrate proportion was reduced in response to treatment addition in cultures (p < 0.001). Anaerobic fungi and Fibrobacter succinogenes abundance were decreased in treatments (p < 0.001). Overall, CH4 production in vitro can be reduced by RB and FRB supplementation as a result of the reduction of fiber-degrading microorganisms and a decrease in gas production.


Subject(s)
Dietary Fiber , Fatty Acids, Volatile , Fermentation , Methane , Oryza , Rumen , Animals , Rumen/microbiology , Rumen/metabolism , Dietary Fiber/metabolism , Methane/metabolism , Fatty Acids, Volatile/metabolism , In Vitro Techniques , Animal Feed , Fibrobacter/metabolism , Propionates/metabolism , Butyrates/metabolism
5.
Microbiol Res ; 285: 127739, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38763016

ABSTRACT

Clostridioides difficile may have a negative impact on gut microbiota composition in terms of diversity and abundance, thereby triggering functional changes supported by the differential presence of genes involved in significant metabolic pathways, such as short-chain fatty acids (SCFA). This work has evaluated shotgun metagenomics data regarding 48 samples from four groups classified according to diarrhea acquisition site (community- and healthcare facility-onset) and positive or negative Clostridioides difficile infection (CDI) result. The metagenomic-assembled genomes (MAGs) obtained from each sample were taxonomically assigned for preliminary comparative analysis concerning differences in composition among groups. The predicted genes involved in metabolism, transport, and signaling remained constant in microbiota members; characteristic patterns were observed in MAGs and genes involved in SCFA butyrate and acetate metabolic pathways for each study group. A decrease in genera and species, as well as relative MAG abundance with the presence of the acetate metabolism-related gene, was evident in the HCFO/- group. Increased antibiotic resistance markers (ARM) were observed in MAGs along with the genes involved in acetate metabolism. The results highlight the need to explore the role of acetate in greater depth as a potential protector of the imbalances produced by CDI, as occurs in other inflammatory intestinal diseases.


Subject(s)
Acetates , Clostridioides difficile , Clostridium Infections , Gastrointestinal Microbiome , Metagenome , Metagenomics , Clostridioides difficile/genetics , Acetates/metabolism , Humans , Clostridium Infections/microbiology , Fatty Acids, Volatile/metabolism , Genome, Bacterial , Butyrates/metabolism , Metabolic Networks and Pathways/genetics , Feces/microbiology , Diarrhea/microbiology
6.
Article in English | MEDLINE | ID: mdl-38739685

ABSTRACT

An oval to rod-shaped, Gram-stain-positive, strictly anaerobic bacterium, designated LFL-14T, was isolated from the faeces of a healthy Chinese woman. Cells of the strain were non-spore-forming, grew optimally at 37 °C (growth range 30-45 °C) and pH 7.0 (growth range 6.0-9.0) under anaerobic conditions in the liquid modified Gifu anaerobic medium (mGAM). The result of 16S rRNA gene-based analysis indicated that LFL-14T shared an identity of 94.7 0% with Eubacterium ventriosum ATCC 27560T, indicating LFL-14T represented a novel taxon. The results of genome-based analysis revealed that the average nucleotide identity (ANI), the digital DNA-DNA hybridisation (dDDH) and average amino acid identity (AAI) between LFL-14T and its phylogenetically closest neighbour, Eubacterium ventriosum ATCC 27560T, were 77.0 %, 24.6 and 70.9 %, respectively, indicating that LFL-14T represents a novel species of the genus Eubacterium. The genome size of LFL-14T was 2.92 Mbp and the DNA G+C content was 33.14 mol%. We analysed the distribution of the genome of LFL-14T in cohorts of healthy individuals, type 2 diabetes patients (T2D) and patients with non-alcoholic fatty liver disease (NAFLD). We found that its abundance was higher in the T2D cohort, but it had a low average abundance of less than 0.2 % in all three cohorts. The percentages of frequency of occurrence in the T2D, healthy and NAFLD cohorts were 48.87 %, 16.72 % and 13.10 % respectively. The major cellular fatty acids of LFL-14T were C16 : 0 (34.4 %), C17 : 0 2-OH (21.4 %) and C14 : 0 (11.7 %). Additionally, the strain contained diphosphatidylglycerol (DPG) and phosphatidylethanolamine (PE), as well as unidentified phospholipids and unidentified glycolipids. The glucose fermentation products of LFL-14T were acetate and butyrate. In summary, On the basis of its chemotaxonomic, phenotypic, phylogenetic and phylogenomic properties, strain LFL-14T (= CGMCC 1.18005T = KCTC 25580T) is identified as representing a novel species of the genus Eubacterium, for which the name Eubacterium album sp. nov. is proposed.


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Eubacterium , Fatty Acids , Feces , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Humans , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Female , Eubacterium/genetics , Eubacterium/isolation & purification , Eubacterium/classification , Feces/microbiology , Butyrates/metabolism , Genome, Bacterial , China , Adult
7.
Gut Microbes ; 16(1): 2350151, 2024.
Article in English | MEDLINE | ID: mdl-38715346

ABSTRACT

The extreme environmental conditions of a plateau seriously threaten human health. The relationship between gut microbiota and human health at high altitudes has been extensively investigated. However, no universal gut microbiota biomarkers have been identified in the plateau population, limiting research into gut microbiota and high-altitude adaptation. 668 16s rRNA samples were analyzed using meta-analysis to reduce batch effects and uncover microbiota biomarkers in the plateau population. Furthermore, the robustness of these biomarkers was validated. Mendelian randomization (MR) results indicated that Tibetan gut microbiota may mediate a reduced erythropoietic response. Functional analysis and qPCR revealed that butyrate may be a functional metabolite in high-altitude adaptation. A high-altitude rat model showed that butyrate reduced intestinal damage caused by high altitudes. According to cell experiments, butyrate may downregulate hypoxia-inducible factor-1α (HIF-1α) expression and blunt cellular responses to hypoxic stress. Our research found universally applicable biomarkers and investigated their potential roles in promoting human health at high altitudes.


Subject(s)
Altitude , Biomarkers , Butyrates , Gastrointestinal Microbiome , Hypoxia-Inducible Factor 1, alpha Subunit , Humans , Tibet , Butyrates/metabolism , Butyrates/analysis , Biomarkers/analysis , Animals , Rats , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , RNA, Ribosomal, 16S/genetics , Bacteria/classification , Bacteria/genetics , Bacteria/metabolism , Bacteria/isolation & purification , Male , Adaptation, Physiological , Mendelian Randomization Analysis
8.
Int J Mol Sci ; 25(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38732048

ABSTRACT

HIV infection results in marked alterations in the gut microbiota (GM), such as the loss of microbial diversity and different taxonomic and metabolic profiles. Despite antiretroviral therapy (ART) partially ablating gastrointestinal alterations, the taxonomic profile after successful new ART has shown wide variations. Our objective was to determine the GM composition and functions in people living with HIV (PLWHIV) under ART in comparison to seronegative controls (SC). Fecal samples from 21 subjects (treated with integrase strand-transfer inhibitors, INSTIs) and 18 SC were included. We employed 16S rRNA amplicon sequencing, coupled with PICRUSt2 and fecal short-chain fatty acid (SCFA) quantification by gas chromatography. The INSTI group showed a decreased α-diversity (p < 0.001) compared to the SC group, at the expense of increased amounts of Pseudomonadota (Proteobacteria), Segatella copri, Lactobacillus, and Gram-negative bacteria. Concurrently, we observed an enrichment in Megasphaera and Butyricicoccus, both SCFA-producing bacteria, and significant elevations in fecal butyrate in this group (p < 0.001). Interestingly, gut dysbiosis in PLWHIV was characterized by a proinflammatory environment orchestrated by Pseudomonadota and elevated levels of butyrate associated with bacterial metabolic pathways, as well as the evident presence of butyrogenic bacteria. The role of this unique GM in PLWHIV should be evaluated, as well as the use of butyrate-based supplements and ART regimens that contain succinate, such as tenofovir disoproxil succinate. This mixed profile is described for the first time in PLWHIV from Mexico.


Subject(s)
Feces , Gastrointestinal Microbiome , HIV Infections , RNA, Ribosomal, 16S , Humans , HIV Infections/microbiology , HIV Infections/drug therapy , Mexico , Female , Male , Adult , Middle Aged , Feces/microbiology , RNA, Ribosomal, 16S/genetics , Dysbiosis/microbiology , Fatty Acids, Volatile/metabolism , Fatty Acids, Volatile/analysis , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Butyrates/metabolism
9.
Environ Microbiol Rep ; 16(3): e13276, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38733087

ABSTRACT

Syntrophic interactions are key in anaerobic food chains, facilitating the conversion of complex organic matter into methane. A typical example involves acetogenic bacteria converting fatty acids (e.g., butyrate and propionate), a process thermodynamically reliant on H2 consumption by microorganisms such as methanogens. While most studies focus on H2-interspecies transfer between these groups, knowledge on acetate cross-feeding in anaerobic systems is lacking. This study investigated butyrate oxidation by co-cultures of Syntrophomonas wolfei and Methanospirillum hungatei, both with and without the addition of the acetate scavenger Methanothrix soehngenii. Growth and gene expression patterns of S. wolfei and M. hungatei were followed in the two conditions. Although butyrate consumption rates remained constant, genes in the butyrate degradation pathway of S. wolfei were less expressed in the presence of M. soehngenii, including genes involved in reverse electron transport. Higher expression of a type IV-pili operon in S. wolfei hints to the potential for direct interspecies electron transfer between S. wolfei and M. soehngenii and an energetically advantageous relationship between the two microorganisms. Overall, the presence of the acetate scavenger M. soehngenii positively influenced the energy metabolism of S. wolfei and highlighted the relevance of including acetate scavengers when investigating syntrophic fatty acid degradation.


Subject(s)
Methanospirillum , Methanospirillum/metabolism , Methanospirillum/genetics , Butyrates/metabolism , Transcriptome , Anaerobiosis , Oxidation-Reduction , Acetates/metabolism , Microbial Interactions , Methane/metabolism , Coculture Techniques , Electron Transport
10.
Brain Behav Immun ; 119: 394-407, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38608743

ABSTRACT

Chronic infection with Toxoplasma gondii (T. gondii) emerges as a risk factor for neurodegenerative diseases in animals and humans. However, the underlying mechanisms are largely unknown. We aimed to investigate whether gut microbiota and its metabolites play a role in T. gondii-induced cognitive deficits. We found that T. gondii infection induced cognitive deficits in mice, which was characterized by synaptic ultrastructure impairment and neuroinflammation in the hippocampus. Moreover, the infection led to gut microbiota dysbiosis, barrier integrity impairment, and inflammation in the colon. Interestingly, broad-spectrum antibiotic ablation of gut microbiota attenuated the adverse effects of the parasitic infection on the cognitive function in mice; cognitive deficits and hippocampal pathological changes were transferred from the infected mice to control mice by fecal microbiota transplantation. In addition, the abundance of butyrate-producing bacteria and the production of serum butyrate were decreased in infected mice. Interestingly, dietary supplementation of butyrate ameliorated T. gondii-induced cognitive impairment in mice. Notably, compared to the healthy controls, decreased butyrate production was observed in the serum of human subjects with high levels of anti-T. gondii IgG. Overall, this study demonstrates that gut microbiota is a key regulator of T. gondii-induced cognitive impairment.


Subject(s)
Cognitive Dysfunction , Dysbiosis , Gastrointestinal Microbiome , Hippocampus , Toxoplasma , Toxoplasmosis , Animals , Mice , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/microbiology , Toxoplasmosis/metabolism , Toxoplasmosis/complications , Dysbiosis/metabolism , Humans , Male , Hippocampus/metabolism , Mice, Inbred C57BL , Fecal Microbiota Transplantation/methods , Butyrates/metabolism , Female , Cognition/physiology
11.
Molecules ; 29(8)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38675716

ABSTRACT

The health benefits of young barley leaves, rich in dietary fiber, have been studied for several decades; however, their beneficial effects on the intestinal microenvironment remain to be elucidated. To investigate the effects of young barley leaf-derived dietary fiber (YB) on the gut microbiota and immunity, mice were fed an AIN-93G diet containing cellulose or YB and subjected to subsequent analysis. The population of MHC-II-positive conventional dendritic cells (cDCs) and CD86 expression in the cDCs of Peyer's patches were elevated in the YB-fed mice. MHC-II and CD86 expression was also elevated in the bone marrow-derived DCs treated with YB. 16S-based metagenomic analysis revealed that the gut microbiota composition was markedly altered by YB feeding. Among the gut microbiota, Lachnospiraceae, mainly comprising butyrate-producing NK4A136 spp., were overrepresented in the YB-fed mice. In fact, fecal butyrate concentration was also augmented in the YB-fed mice, which coincided with increased retinaldehyde dehydrogenase (RALDH) activity in the CD103+ cDCs of the mesenteric lymph nodes. Consistent with elevated RALDH activity, the population of colonic IgA+ plasma cells was higher in the YB-fed mice than in the parental control mice. In conclusion, YB has beneficial effects on the gut microbiota and intestinal immune system.


Subject(s)
Dietary Fiber , Gastrointestinal Microbiome , Hordeum , Plant Leaves , Animals , Gastrointestinal Microbiome/drug effects , Hordeum/chemistry , Dietary Fiber/pharmacology , Plant Leaves/chemistry , Mice , Retinal Dehydrogenase/metabolism , Butyrates/metabolism , Feces/microbiology
12.
Nutrients ; 16(8)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38674791

ABSTRACT

Sleep deprivation (SD) leads to impaired intestinal barrier function and intestinal flora disorder, especially a reduction in the abundance of the next generation of probiotic Faecalibacterium prausnitzii (F. prausnitzii). However, it remains largely unclear whether F. prausnitzii can ameliorate SD-induced intestinal barrier damage. A 72 h SD mouse model was used in this research, with or without the addition of F. prausnitzii. The findings indicated that pre-colonization with F. prausnitzii could protect against tissue damage from SD, enhance goblet cell count and MUC2 levels in the colon, boost tight-junction protein expression, decrease macrophage infiltration, suppress pro-inflammatory cytokine expression, and reduce apoptosis. We found that the presence of F. prausnitzii helped to balance the gut microbiota in SD mice by reducing harmful bacteria like Klebsiella and Staphylococcus, while increasing beneficial bacteria such as Akkermansia. Ion chromatography analysis revealed that F. prausnitzii pretreatment increased the fecal butyrate level in SD mice. Overall, these results suggested that incorporating F. prausnitzii could help reduce gut damage caused by SD, potentially by enhancing the intestinal barrier and balancing gut microflora. This provides a foundation for utilizing probiotics to protect against intestinal illnesses.


Subject(s)
Dysbiosis , Faecalibacterium prausnitzii , Gastrointestinal Microbiome , Intestinal Mucosa , Probiotics , Sleep Deprivation , Animals , Sleep Deprivation/complications , Mice , Probiotics/pharmacology , Probiotics/administration & dosage , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Male , Feces/microbiology , Mice, Inbred C57BL , Dietary Supplements , Disease Models, Animal , Mucin-2/metabolism , Butyrates/metabolism , Colon/microbiology , Colon/metabolism
13.
Physiol Genomics ; 56(6): 426-435, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38557279

ABSTRACT

Short-chain fatty acids (SCFAs) produced by the gut bacteria have been associated with cardiovascular dysfunction in humans and rodents. However, studies exploring effects of SCFAs on cardiovascular parameters in the zebrafish, an increasingly popular model in cardiovascular research, remain limited. Here, we performed fecal bacterial 16S sequencing and gas chromatography/mass spectrometry (GC-MS) to determine the composition and abundance of gut microbiota and SCFAs in adult zebrafish. Following this, the acute effects of major SCFAs on heart rate and vascular tone were measured in anesthetized zebrafish larvae using fecal concentrations of butyrate, acetate, and propionate. Finally, we investigated if coincubation with butyrate may lessen the effects of angiotensin II (ANG II) and phenylephrine (PE) on vascular tone in anesthetized zebrafish larvae. We found that the abundance in Proteobacteria, Firmicutes, and Fusobacteria phyla in the adult zebrafish resembled those reported in rodents and humans. SCFA levels with highest concentration of acetate (27.43 µM), followed by butyrate (2.19 µM) and propionate (1.65 µM) were observed in the fecal samples of adult zebrafish. Immersion in butyrate and acetate produced a ∼20% decrease in heart rate (HR), respectively, with no observed effects of propionate. Butyrate alone also produced an ∼25% decrease in the cross-sectional width of the dorsal aorta (DA) at 60 min (*P < 0.05), suggesting compensatory vasoconstriction, with no effects of either acetate or propionate. In addition, butyrate significantly alleviated the decrease in DA cross-sectional width produced by both ANG II and PE. We demonstrate the potential for zebrafish in investigation of host-microbiota interactions in cardiovascular health.NEW & NOTEWORTHY We highlight the presence of a core gut microbiota and demonstrate in vivo short-chain fatty acid production in adult zebrafish. In addition, we show cardio-beneficial vasoactive and chronotropic properties of butyrate, and chronotropic properties of acetate in anesthetized zebrafish larvae.


Subject(s)
Fatty Acids, Volatile , Feces , Gastrointestinal Microbiome , Heart Rate , Larva , Zebrafish , Animals , Zebrafish/microbiology , Gastrointestinal Microbiome/drug effects , Fatty Acids, Volatile/metabolism , Heart Rate/drug effects , Feces/microbiology , Butyrates/metabolism , Butyrates/pharmacology , Angiotensin II/metabolism , Angiotensin II/pharmacology , Bacteria/drug effects , Phenylephrine/pharmacology , Acetates/pharmacology , Acetates/metabolism , RNA, Ribosomal, 16S/genetics
14.
Cell Rep Med ; 5(4): 101488, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38565146

ABSTRACT

Most recurrences of lung cancer (LC) occur within 3 years after surgery, but the underlying mechanism remains unclear. Here, we collect LC tissues with shorter (<3 years, recurrence group) and longer (>3 years, non-recurrence group) recurrence-free survival. By using 16S sequencing, we find that intratumor microbiome diversity is lower in the recurrence group and butyrate-producing bacteria are enriched in the recurrence group. The intratumor microbiome signature and circulating microbiome DNA can accurately predict LC recurrence. We prove that intratumor injection of butyrate-producing bacteria Roseburia can promote subcutaneous tumor growth. Mechanistically, bacteria-derived butyrate promotes LC metastasis by increasing expression of H19 in tumor cells through inhibiting HDAC2 and increasing H3K27 acetylation at the H19 promoter and inducing M2 macrophage polarization. Depletion of macrophages partially abolishes the metastasis-promoting effect of butyrate. Our results provide evidence for the cross-talk between the intratumor microbiome and LC metastasis and suggest the potential prognostic and therapeutic value of the intratumor microbiome.


Subject(s)
Lung Neoplasms , Microbiota , Humans , Lung Neoplasms/pathology , Butyrates/metabolism , Neoplasm Recurrence, Local/metabolism , Macrophages
15.
Neurochem Int ; 176: 105745, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38641025

ABSTRACT

Maintaining an optimum microbial community within the gastrointestinal tract is intricately linked to human metabolic, immune and brain health. Disturbance to these microbial populations perturbs the production of vital bioactive compounds synthesised by the gut microbiome, such as short-chain fatty acids (SCFAs). Of the SCFAs, butyrate is known to be a major source of energy for colonocytes and has valuable effects on the maintenance of intestinal epithelium and blood brain barrier integrity, gut motility and transit, anti-inflammatory effects, and autophagy induction. Inducing endogenous butyrate production is likely to be beneficial for gut-brain homeostasis and for optimal neuronal function. For these reasons, butyrate has gained interest as a potential therapy for not only metabolic and immunological disorders, but also conditions related to the brain, including neurodegenerative diseases. While direct and indirect sources of butyrate, including prebiotics, probiotics, butyrate pro-drugs and glucosidase inhibitors, offer a promising therapeutic avenue, their efficacy and dosage in neurodegenerative conditions remain largely unknown. Here, we review current literature on effects of butyrate relevant to neuronal function, the impact of butyrate in a range of neurodegenerative diseases and related treatments that may have potential for the treatment of neurodegenerative diseases.


Subject(s)
Butyrates , Gastrointestinal Microbiome , Neurodegenerative Diseases , Humans , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Animals , Butyrates/therapeutic use , Butyrates/pharmacology , Butyrates/metabolism , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/physiology , Probiotics/therapeutic use
16.
BMC Microbiol ; 24(1): 83, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38468200

ABSTRACT

BACKGROUND: The interplay between gut microbiota (GM) and the metabolization of dietary components leading to the production of short-chain fatty acids (SCFAs) is affected by a range of factors including colonic pH and carbohydrate source. However, there is still only limited knowledge on how the GM activity and metabolite production in the gastrointestinal tract could be influenced by pH and the pH gradient increases along the colon. RESULTS: Here we investigate the effect of pH gradients corresponding to levels typically found in the colon on GM composition and metabolite production using substrates inulin, lactose, galactooligosaccharides (GOS), and fructooligosaccharide (FOS) in an in vitro colon setup. We investigated 3 different pH regimes (low, 5.2 increasing to 6.4; medium, 5.6 increasing to 6.8 and high, 6.0 increasing to 7.2) for each fecal inoculum and found that colonic pH gradients significantly influenced in vitro simulated GM structure, but the influence of fecal donor and substrate was more pronounced. Low pH regimes strongly influenced GM with the decreased relative abundance of Bacteroides spp. and increased Bifidobacterium spp. Higher in vitro simulated colonic pH promoted the production of SCFAs in a donor- and substrate-dependent manner. The butyrate producer Butyricimonas was enriched at higher pH conditions, where also butyrate production was increased for inulin. The relative abundance of Phascolarctobacterium, Bacteroides, and Rikenellaceae also increased at higher colonic pH, which was accompanied by increased production of propionate with GOS and FOS as substrates. CONCLUSIONS: Together, our results show that colonic substrates such as dietary fibres influence GM composition and metabolite production, not only by being selectively utilized by specific microbes, but also because of their SCFA production, which in turn also influences colonic pH and overall GM composition and activity. Our work provides details about the effect of the gradients of rising pH from the proximal to distal colon on fermenting dietary substrates in vitro and highlights the importance of considering pH in GM research.


Subject(s)
Inulin , Prebiotics , Prebiotics/analysis , Inulin/metabolism , Proton-Motive Force , Fermentation , Fatty Acids, Volatile/metabolism , Butyrates/metabolism , Feces/microbiology , Bacteroidetes
17.
Food Funct ; 15(6): 3186-3198, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38441170

ABSTRACT

The modern diet delivers nearly equal amounts of carbohydrates and protein into the colon representing an important protein increase compared to past higher fiber diets. At the same time, plant-based protein foods have become increasingly popular, and these sources of protein are generally less digestible than animal protein sources. As a result, a significant amount of protein is expected to reach the colon and be available for fermentation by gut microbiota. While studies on diet-microbiota interventions have mainly focused on carbohydrate fermentation, limited attention has been given to the role of protein or protein-fiber mixtures as fermentation substrates for the colonic microbiota. In this study, we aimed to investigate: (1) how changing the ratio of protein to fiber substrates affects the types and quantities of gut microbial metabolites and bacteria; and (2) how the specific fermentation characteristics of different types of fiber might influence the utilization of protein by gut microbes to produce beneficial short chain fatty acids. Our results revealed that protein fermentation in the gut plays a crucial role in shaping the overall composition of microbiota communities and their metabolic outputs. Surprisingly, butyrate production was maintained or increased when fiber and protein were combined, and even when pure protein samples were used as substrates. These findings suggest that indigestible protein in fiber-rich substrates may promote the production of microbial butyrate perhaps including the later stages of fermentation in the large intestine.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Animals , Dietary Fiber/analysis , Butyrates/metabolism , Fermentation , Fatty Acids, Volatile/metabolism , Feces/microbiology
18.
PLoS One ; 19(3): e0298930, 2024.
Article in English | MEDLINE | ID: mdl-38507436

ABSTRACT

The rumen represents a dynamic microbial ecosystem where fermentation metabolites and microbial concentrations change over time in response to dietary changes. The integration of microbial genomic knowledge and dynamic modelling can enhance our system-level understanding of rumen ecosystem's function. However, such an integration between dynamic models and rumen microbiota data is lacking. The objective of this work was to integrate rumen microbiota time series determined by 16S rRNA gene amplicon sequencing into a dynamic modelling framework to link microbial data to the dynamics of the volatile fatty acids (VFA) production during fermentation. For that, we used the theory of state observers to develop a model that estimates the dynamics of VFA from the data of microbial functional proxies associated with the specific production of each VFA. We determined the microbial proxies using CowPi to infer the functional potential of the rumen microbiota and extrapolate their functional modules from KEGG (Kyoto Encyclopedia of Genes and Genomes). The approach was challenged using data from an in vitro RUSITEC experiment and from an in vivo experiment with four cows. The model performance was evaluated by the coefficient of variation of the root mean square error (CRMSE). For the in vitro case study, the mean CVRMSE were 9.8% for acetate, 14% for butyrate and 14.5% for propionate. For the in vivo case study, the mean CVRMSE were 16.4% for acetate, 15.8% for butyrate and 19.8% for propionate. The mean CVRMSE for the VFA molar fractions were 3.1% for acetate, 3.8% for butyrate and 8.9% for propionate. Ours results show the promising application of state observers integrated with microbiota time series data for predicting rumen microbial metabolism.


Subject(s)
Microbiota , Propionates , Female , Animals , Cattle , Propionates/metabolism , Fermentation , Rumen/metabolism , Time Factors , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism , Fatty Acids, Volatile/metabolism , Acetates/metabolism , Butyrates/metabolism , Diet/veterinary , Animal Feed/analysis
20.
J Anim Sci ; 1022024 Jan 03.
Article in English | MEDLINE | ID: mdl-38513071

ABSTRACT

This experiment was conducted to evaluate the effects of including a mixed-dimensional attapulgite clay (MDA) into a naturally moldly diet for Hu lambs. Fifty male Hu lambs with similar initial body weight (28.24 ±â€…1.80 kg) were randomly allocated into five dietary treatments: a basal diet containing naturally occurring mycotoxins with 0, 0.5, 1.0, and 2.0 kg/t MDA, and basal diet with a commercial mycotoxin adsorbent Solis with montmorillonite as the major component at 1 kg/t. Both MDA and Solis increased average daily gain (ADG) and dry matter intake (DMI; P ≤ 0.004), and there was no difference in growth performance between MDA and Solis (P ≥ 0.26). The final body weight, DMI, and ADG were linearly increased with increasing MDA supplementation (P < 0.01). Lambs treated with both MDA and Solis demonstrated greater apparent digestibility of dry matter (DM), organic matter (OM), and energy compared with the control group (P ≤ 0.03), and there were no differences in nutrient digestibilities between MDA and Solis (P ≥ 0.38). Digestibility of CP was linearly increased with the increasing MDA supplementation (P = 0.01). Neither MDA nor Solis affected rumen total volatile fatty acid (TVFA) concentration (P ≥ 0.39), but decreased the acetate-to-propionate ratio and molar proportion of n-butyrate (P ≤ 0.01), and MDA also increased the concentration of ammonia (P = 0.003). Besides, increasing MDA supplementation linearly reduced the acetate-to-propionate ratio and molar proportion of n-butyrate (P = 0.01), but linearly and quadratically increased the concentration of ammonia (P ≥ 0.003). These results showed that the incorporation of MDA into a naturally moldy diet of Hu lambs yielded comparable results to the Solis product, with higher growth performance and nutrient digestibility but lower acetate-to-propionate ratio observed. In conclusion, including ≥ 1 kg/t of MDA in high mycotoxin risk diets for growing lambs improves feed intake and rumen fermentation.


The issue of mycotoxin-contaminated animal feed has consistently presented a significant challenge in relation to animal health and production. The mixed-dimensional attapulgite clay (MDA) has been proven effective in binding polar mycotoxins such as aflatoxin, while also effectively adsorbing hydrophobic or weakly polar mycotoxins such as zearalenone (ZEN) and ochratoxin. Therefore, this study was undertaken to assess the impact of MDA inclusion in mycotoxin-contaminated diets on performance and rumen fermentation variables in lambs. The results indicated that MDA not only significantly improved the growth performance and nutrient digestibility of Hu lambs but also enhanced the molar proportion of propionate and ammonia concentration, and reduced the acetate to propionate ratio and the molar proportion of n-butyrate.


Subject(s)
Magnesium Compounds , Mycotoxins , Rumen , Silicon Compounds , Sheep , Animals , Male , Clay , Rumen/metabolism , Propionates/metabolism , Fermentation , Ammonia/metabolism , Digestion , Diet/veterinary , Sheep, Domestic , Eating , Acetates/metabolism , Butyrates/metabolism , Body Weight , Animal Feed/analysis
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