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Biochemical characterization of the first step in sulfonolipid biosynthesis in Alistipes finegoldii.The Journal of Biological Chemistry Aug 2022Sulfonolipids are unusual lipids found in the outer membranes of Gram-negative bacteria in the phylum Bacteroidetes. Sulfonolipid and its deacylated derivative, capnine,...
Sulfonolipids are unusual lipids found in the outer membranes of Gram-negative bacteria in the phylum Bacteroidetes. Sulfonolipid and its deacylated derivative, capnine, are sulfur analogs of ceramide-1-phosphate and sphingosine-1-phosphate, respectively; thus, sulfonolipid biosynthesis is postulated to be similar to the sphingolipid biosynthetic pathway. Here, we identify the first enzyme in sulfonolipid synthesis in Alistipes finegoldii as the product of the alfi_1224 gene, cysteate acyl-acyl carrier protein (ACP) transferase (SulA). We show SulA catalyzes the condensation of acyl-ACP and cysteate (3-sulfo-alanine) to form 3-ketocapnine. Acyl-CoA is a poor substrate. We show SulA has a bound pyridoxal phosphate (PLP) cofactor that undergoes a spectral redshift in the presence of cysteate, consistent with the transition of the lysine-aldimine complex to a substrate-aldimine complex. Furthermore, the SulA crystal structure shows the same prototypical fold found in bacterial serine palmitoyltransferases (Spts), enveloping the PLP cofactor bound to Lys251. We observed the SulA and Spt active sites are identical except for Lys281 in SulA, which is an alanine in Spt. Additionally, SulA(K281A) is catalytically inactive but binds cysteate and forms the external aldimine normally, highlighting the structural role of the Lys281 side chain in walling off the active site from bulk solvent. Finally, the electropositive groove on the protein surface adjacent to the active site entrance provides a landing pad for the electronegative acyl-ACP surface. Taken together, these data identify the substrates, products, and mechanism of SulA, the PLP-dependent condensing enzyme that catalyzes the first step in sulfonolipid synthesis in a gut commensal bacterium.
Topics: Acyl Carrier Protein; Alanine; Bacteroidetes; Cysteic Acid; Lipids; Pyridoxal Phosphate
PubMed: 35760102
DOI: 10.1016/j.jbc.2022.102195 -
Frontiers in Microbiology 2021Making full use of high fiber and low-cost crop coproducts is helpful to alleviate the situation of people and livestock competing for crops. Digestion of dietary fibers...
Making full use of high fiber and low-cost crop coproducts is helpful to alleviate the situation of people and livestock competing for crops. Digestion of dietary fibers in pigs is mainly through microbial fermentation in the large intestine. To reveal microbiota related to fiber digestion in pigs, fecal samples have been collected from 274 healthy female Suhuai pigs at 160 days of age under the same feeding conditions and have measured apparent neutral detergent fiber (NDF) and acid detergent fiber (ADF) digestibility. Samples from Suhuai pigs with extreme high and low apparent NDF digestibility and extreme high and low apparent ADF digestibility were subjected to shotgun metagenomic sequencing. At the species level, 62 microbial species in H_NDF group and 54 microbial species in H_ADF group were related to high fiber digestibility. Among them, and sp. may be new types of microorganisms associated with fiber digestion. In addition, we found that more abundant GH5 and GH48 family (contribute to cellulose degradation) genes, GH39 and GH53 family (contribute to hemicellulose degradation) genes in microorganisms may contribute to the higher apparent NDF digestibility of pigs, and more abundant GH3 and GH9 family (contribute to cellulose degradation) genes in microorganisms may contribute to the higher apparent ADF digestibility of pigs. The abundance of AA4 family (helps in lignin degradation) genes in H_NDF and H_ADF groups was significantly higher than that in L_NDF and L_ADF groups, respectively ( < 0.05). Three pathways in H_NDF group and four pathways in H_ADF group are important pathways associated with degradation of non-starch polysaccharides, and their relative abundance is significantly higher than that in L_NDF and L_ADF groups, respectively. Gut microbiota of Suhuai pigs with high apparent fiber digestibility had higher abundance of genes and microbiota related to fiber digestion and may have stronger fiber digestion potential compared with low apparent fiber digestibility group. This study revealed that the characteristics of gut microbiota and microbial gene functions of pigs with high fiber apparent digestibility, which provided a theoretical basis and reference for further understanding the impact of gut microbiota on fiber digestibility of pigs.
PubMed: 34867862
DOI: 10.3389/fmicb.2021.746717 -
BMC Medicine Oct 2022Extraintestinal symptoms are common in inflammatory bowel diseases (IBD) and include depression and fatigue. These are highly prevalent especially in active disease,...
BACKGROUND
Extraintestinal symptoms are common in inflammatory bowel diseases (IBD) and include depression and fatigue. These are highly prevalent especially in active disease, potentially due to inflammation-mediated changes in the microbiota-gut-brain axis. The aim of this study was to investigate the associations between structural and functional microbiota characteristics and severity of fatigue and depressive symptoms in patients with active IBD.
METHODS
We included clinical data of 62 prospectively enrolled patients with IBD in an active disease state. Patients supplied stool samples and completed the questionnaires regarding depression and fatigue symptoms. Based on taxonomic and functional metagenomic profiles of faecal gut microbiota, we used Bayesian statistics to investigate the associative networks and triangle motifs between bacterial genera, functional modules and symptom severity of self-reported fatigue and depression.
RESULTS
Associations with moderate to strong evidence were found for 3 genera (Odoribacter, Anaerotruncus and Alistipes) and 3 functional modules (pectin, glycosaminoglycan and central carbohydrate metabolism) with regard to depression and for 4 genera (Intestinimonas, Anaerotruncus, Eubacterium and Clostridiales g.i.s) and 2 functional modules implicating amino acid and central carbohydrate metabolism with regard to fatigue.
CONCLUSIONS
This study provides the first evidence of association triplets between microbiota composition, function and extraintestinal symptoms in active IBD. Depression and fatigue were associated with lower abundances of short-chain fatty acid producers and distinct pathways implicating glycan, carbohydrate and amino acid metabolism. Our results suggest that microbiota-directed therapeutic approaches may reduce fatigue and depression in IBD and should be investigated in future research.
Topics: Amino Acids; Bayes Theorem; Depression; Fatigue; Feces; Glycosaminoglycans; Humans; Inflammatory Bowel Diseases; Metagenomics; Microbiota; Pectins
PubMed: 36244970
DOI: 10.1186/s12916-022-02550-7 -
Frontiers in Cellular and Infection... 2022The brain development of preterm infants is easily affected by various adverse extrauterine factors and complications, resulting in abnormal neurological and cognitive...
BACKGROUND
The brain development of preterm infants is easily affected by various adverse extrauterine factors and complications, resulting in abnormal neurological and cognitive development. Recent studies have found that there is a significant correlation between intestinal microbial changes and cognitive behavior. Nevertheless, the correlation between the cognitive impairment and abnormal changes of intestinal microflora in the preterm newborn has been rarely elucidated.
AIM
To analyze the differences of fecal intestinal flora, short chain fatty acids (SCFAs) and microbiota-gut-brain axis (MGBA)-related serum factors between preterm birth with and without cognitive impairment.
METHODS
Healthy female rats (body weight 410 ± 40 g) of 16-17 days of gestation were selected for the establishment of preterm cognitive impairment model and screened by Morris water maze navigation experiments. The pathological change of rat hippocampus was confirmed by HE staining. The abundance of fecal intestinal microflora was determined by 16sRNA sequencing, while the contents of fecal SCFAs were examined by gas chromatography.
RESULTS
Compared with the control group, the cognitive impairment group had decreased abundance and diversity of intestinal microflora and increased abundance of at the level of phylum. While the abundances of , , , and decreased significantly at the level of order, family, and genus, the abundances of , , , and increased significantly. Moreover, the levels of total SCFAs and acetic acid in the disease group were significantly lower. The fecal abundance of acetic acid was positively correlated with that of or , and negatively correlated with that of , and in disease rats. Furthermore, cognitive impairment caused significantly decreased levels of 5-HT, GABA, and BDNF, and increased levels of GR, CRH, IL-6, and TNF-α in rat blood.
CONCLUSION
Alterations in intestinal microflora structure and the abundances of SCFAs contributed substantially to the cognitive impairment in preterm rats, which was associated with significant changes in MGBA-related soluble factors.
Topics: Animals; Cognitive Dysfunction; Fatty Acids, Volatile; Female; Gastrointestinal Microbiome; Humans; Infant, Newborn; Infant, Premature; Premature Birth; Rats
PubMed: 36061856
DOI: 10.3389/fcimb.2022.945851 -
Journal of Cancer 2022Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumour with a poor prognosis and a high mortality rate. It is of great significance to explore sensitive or...
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumour with a poor prognosis and a high mortality rate. It is of great significance to explore sensitive or specific biomarkers for early diagnosis and prognosis. We first examined the metabolome and gut microbiota of resectable and unresectable PDAC patients to comprehensively investigate the characteristics of PDAC at different stages of progression. At the genus level, we found that the relative abundances of Alistipes, Anaerostipes, Faecalibacterium and Parvimonas were reduced in unresectable PDAC patients, whereas Pseudonocardia, Cloacibacterium, Mucispirillum, and Anaerotruncus were increased. Metabolomics analysis showed that the main changed metabolites were amino acids, carnitine derivatives, lipids and fatty acids. ROC analysis showed that Oleic acid, Linoleic acid, Palmitic acid, Linoelaidyl carnitine, 2-Octenedioic acid, 3R, 7R-1,3,7-Octanetriol, LysoPE (P-16:0/0:0) and 3-Hydroxyanthranilic acid had high AUC values (>0.9). Function and network analyses showed that these altered metabolites correlated with NF-kappa B signalling, the FXR/RXR pathway, mitochondrial dysfunction, mTOR signalling and IL-6 signalling. In particular, the abundance of Palmitic acid, Oleic acid, Linoelaidyl carnitine and 2-Octenedioic acid positively correlated with but negatively correlated with Meanwhile,We also found that PE (22:6 (4Z, 7z, 10z, 13z, 16Z, 19Z)/p-18:1 (11z)), (3R, 7R) - 1,3,7-octanetriol and linoelaidyl carnitine were positively correlated with the survival time of patients.These findings may be helpful for the differentiation of resectable and unresectable PDAC based on changes in intestinal flora and metabolites at different stages of PDAC. This study also provides a strategy for preventing the deterioration of PDAC by regulating the gut microbiota and metabolism.
PubMed: 35371330
DOI: 10.7150/jca.52943 -
Frontiers in Microbiology 2022Diabetic retinopathy (DR) is one of the most common complications of type 2 diabetes mellitus. The current study investigates the composition, structure, and function of...
OBJECTIVE
Diabetic retinopathy (DR) is one of the most common complications of type 2 diabetes mellitus. The current study investigates the composition, structure, and function of gut microbiota in DR patients and explores the correlation between gut microbiota and clinical characteristics of DR.
METHODS
A total of 50 stool samples were collected from 50 participants, including 25 DR patients and 25 healthy controls (HCs). 16S ribosomal RNA gene sequencing was used to analyze the gut microbial composition in these two groups. DNA was extracted from the fecal samples using the MiSeq platform.
RESULTS
The microbial structure and composition of DR patients were different from that of HCs. The microbial richness of gut microbiota in DR was higher than that of normal individuals. The alterations of microbiome of DR patients were associated with disrupted Firmicutes, Bacteroidetes, Synergistota, and Desulfobacterota phyla. In addition, increased levels of , , _group, , and , and decreased levels of , _group, , , , , and genera were observed in the DR groups. Additionally, a stochastic forest model was developed to identify a set of biomarkers with seven bacterial genera that can differentiate patients with DR from those HC. The microbial communities exhibited varied functions in these two groups because of the alterations of the above-mentioned bacterial genera.
CONCLUSION
The altered composition and function of gut microbiota in DR patients indicated that gut microbiome could be used as non-invasive biomarkers, improve clinical diagnostic methods, and identify putative therapeutic targets for DR.
PubMed: 36081798
DOI: 10.3389/fmicb.2022.926926 -
Frontiers in Nutrition 2022This study was aimed to evaluate the effects of low-carbohydrate diet (LC) and incorporated high-intensity interval training (HIIT) or moderate-intensity continuous...
OBJECTIVE
This study was aimed to evaluate the effects of low-carbohydrate diet (LC) and incorporated high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) on gut microbiota, and the associations between changes in gut microbiota and cardiometabolic health-related profiles.
METHODS
Fifty overweight/obese Chinese females (age 22.2 ± 3.3 years, body mass index 25.1 ± 3.1 kg/m) were randomized to the groups of LC, LC and HIIT (LC-HIIT, 10 repetitions of 6-s sprints and 9-s rest), and LC and MICT group (LC-MICT, cycling at 50-60% V̇O for 30 min). The LC-HIIT and LC-MICT experienced 20 training sessions over 4 weeks.
RESULTS
The 4-week LC intervention with/without additional training failed to change the Shannon, Chao 1, and Simpson indexes ( > 0.05), LC increased genus, and LC-HIIT reduced genus after intervention ( < 0.05). Groups with extra exercise training increased short-chain fatty acid-producing genus ( < 0.05) and reduced type 2 diabetes-related genus ( < 0.05) compared to LC. ( = -0.335) and ( = 0.334) were associated with changes in body composition ( < 0.05). Changes in , , and genera were positively associated with blood pressure (BP) changes ( = 0.392-0.445, < 0.05), whereas the changes in , , and genera were negatively associated with BP changes ( = -0.567 to -0.362, < 0.05).
CONCLUSION
LC intervention did not change the α-diversity and overall structure of gut microbiota. Combining LC with exercise training may have additional benefits on gut physiology. Specific microbial genera were associated with LC- and exercise-induced regulation of cardiometabolic health.
PubMed: 35592627
DOI: 10.3389/fnut.2022.884550 -
Frontiers in Microbiology 2023Psychological stress can induce affective disorders. Gut microbiota plays a vital role in emotional function regulation; however, the association between gut microbiota...
INTRODUCTION
Psychological stress can induce affective disorders. Gut microbiota plays a vital role in emotional function regulation; however, the association between gut microbiota and psychological stress is poorly understood. We investigated effects of psychological stress on the gut microbiome and fecal metabolites and assessed the relationship between affective disorder behavior and altered fecal microbiota.
METHODS
A psychological stress model was established in C57BL/6J mice using a communication box. Sucrose preference test, forced swim test, and open field test helped assess anxiety- and depression-like behaviors. Fecal microbiota transplantation (FMT) was conducted using fecal samples from stressed and non-stressed mice. Moreover, 16S rRNA gene sequencing and untargeted metabolomics were performed.
RESULTS
After stress exposure for 14 days, a significant increase in anxiety- and depression-like behaviors was observed. FMT of "affective disorder microbiota" from psychologically stressed mice increased stress sensitivity relative to FMT of "normal microbiota" from non-stressed mice. 16S rRNA gene sequencing revealed decreased abundance of , , and and increased abundance of Parasutterella and in stressed mice; furthermore, stressed mice showed differential metabolite profiles. KEGG pathway analysis indicated that differential metabolites were chiefly involved in the downregulated pathways of α-linolenic acid metabolism, taste transduction, and galactose metabolism. and were mainly positively correlated and was mainly negatively correlated with diverse metabolites.
DISCUSSION
Our findings suggest that gut microbiome dysbiosis contributes to affective disorder development in response to psychological stress.
PubMed: 37213506
DOI: 10.3389/fmicb.2023.1124454 -
Medicine and Science in Sports and... Apr 2023We aimed to assess whether total daily physical activity (PA), PA intensities, sedentary time (ST), and prolonged ST are associated with differences in the gut...
PURPOSE
We aimed to assess whether total daily physical activity (PA), PA intensities, sedentary time (ST), and prolonged ST are associated with differences in the gut microbiota composition or short-chain fatty acid (SCFA) profile of adults with overweight or obesity.
METHODS
Cross-sectional associations between total daily PA (counts per minute), PA intensities (light and moderate-to-vigorous (MVPA)), ST, prolonged ST, and fecal microbiota composition were assessed in adults ( n = 124) between 25 and 45 yr of age with body mass index ≥25 kg·m -2 . Fecal microbiota composition was assessed with 16S rRNA gene sequencing. Daily PA and ST were measured with a hip-worn ActiGraph wGT3X-BT accelerometer.
RESULTS
Daily PA volume and intensity were positively associated with relative abundance of Faecalibacterium ( P = 0.04) and negatively associated with the abundances of Alistipes , Parabacteroides , and Gemmiger ( P = 0.003-0.04) as well as the concentrations of acetate, butyrate, and total SCFA (all P = 0.04). Conversely, ST was negatively associated with abundance of Faecalibacterium but positively associated with the abundances of taxa, including Ruminococcaceae, Parabacteroides , Alistipes , and Gemmiger . Clustering of participants based on whether they met PA recommendations suggested that SCFA profiles differed between individuals who did and did not meet PA recommendations. K-means clustering based on percent of time spent in MVPA and ST also identified differences in fecal microbiota composition between cluster 1 (lower MVPA, higher ST) and cluster 2 (higher MVPA, lower ST), including a higher abundance of Alistipes in cluster 1.
CONCLUSIONS
The current analysis suggests a beneficial association of daily PA on the fecal microbiota and a negative association of ST, particularly with respect to the associations of these variables with the genera Faecalibacterium , a butyrate-producing taxon.
Topics: Humans; Adult; Overweight; Cross-Sectional Studies; RNA, Ribosomal, 16S; Exercise; Obesity; Gastrointestinal Microbiome; Fatty Acids, Volatile; Butyrates; Accelerometry
PubMed: 36728974
DOI: 10.1249/MSS.0000000000003096 -
Journal of Microbiology and... Feb 2020The differences between luminal microbiota (LM) and mucosal microbiota (MAM) were little known, especially in duodenum. In this study, LM and MAM in colon and duodenum...
The differences between luminal microbiota (LM) and mucosal microbiota (MAM) were little known, especially in duodenum. In this study, LM and MAM in colon and duodenum of mice were investigated through 16S rRNA high-throughput sequencing. The lowest bacterial diversity and evenness were observed in duodenal LM (D_LM), followed by duodenal MAM (D_MAM). Meanwhile, the bacterial diversity and evenness were obviously increased in D_MAM than these in D_LM, while no significant difference was observed between colonic MAM (C_MAM) and colonic LM (C_LM). PCoA analysis also showed that bacterial communities of LM and MAM in duodenum were completely separated, while these in colon overlapped partly. The ratio of Firmicutes to Bacteroidetes (F/B) in D_MAM was significantly higher than that in D_LM. was largely enriched and was the characteristic bacteria in D_LM. The characteristic bacteria in D_MAM were , and , while in C_LM they were _6, _9, _UCG_007 and _UCG_010, and in C_MAM they were _NK4A136, , , and . The networks showed that more interactions existed in colonic microbiota (24 nodes and 74 edges) than in duodenal microbiota (17 nodes and 29 edges). The 16S rDNA function prediction results indicated that bigger differences of function exist between LM and MAM in duodenum than these in colon. In conclusion, microbiota from intestinal luminal content and mucosa were different both in colon and in duodenum, and bacteria in colon interacted with each other much more closely than those in duodenum.
Topics: Animals; Bacteria; Biodiversity; Colon; Computational Biology; Duodenum; High-Throughput Nucleotide Sequencing; Intestinal Mucosa; Metagenome; Metagenomics; Mice; Microbiota; Mucous Membrane; Organ Specificity
PubMed: 31635444
DOI: 10.4014/jmb.1908.08037