Association between Fecal Short-Chain Fatty Acid Levels, Diet, and Body Mass Index in Patients with Inflammatory Bowel Disease

Disturbances in the production of bacterial metabolites in the intestine have been reported in diseases associated with dysbiosis, such as inflammatory bowel diseases (IBDs) that include two conditions: Crohn disease (CD) and ulcerative colitis (UC). Short-chain fatty acids (SCFAs) are the main dietary-fiber-derived bacterial metabolites associated with the course of intestinal inflammation. In this study, we assessed the relationship between body mass index (BMI), the type of diet used, and changes in fecal SCFA levels in patients with IBD. We performed nutritional assessments using a nutritional questionnaire and determined fecal SCFA levels in 43 patients with UC, 18 patients with CD, and 16 controls. Our results revealed that subjects with a BMI > 24.99 kg/m2 had higher levels of isobutyric acid, whereas those with a BMI < 18.5 kg/m2 had lower level of butyric, isovaleric, and propionic acids. Furthermore, we observed higher levels of valeric acid in controls than in IBD patients. We did not reveal a relationship between a specific SCFA and the type of diet, but eating habits appear to be related to the observed changes in the SCFA profile depending on BMI. In conclusion, we demonstrated that BMI is associated with SCFA levels in patients with IBD.

Configuration of the Volatile Aromatic Profile of Carob Powder Milled From Pods of Genetic Variants Harvested at Progressive Stages of Ripening From High and Low Altitudes

Carob powder is increasingly valued as a substitute for cocoa and as a flavor-enhancing component of processed foods. However, little is known about the impact of preharvest factors such as fruit maturity, genotype and altitude on its volatile organic compounds (VOCs) composition. The current study examined the VOCs composition of powder milled from pods of two genotypes cultivated at 15 and 510 m altitude and harvested at six progressive stages of maturity, ranging from fully developed immature green (RS1) to late ripe (RS6). Fifty-six VOCs categorized into acids, esters, aldehydes, ketones, alcohols, furans, and alkanes were identified through HS-SPME GC-MS analysis. Maturity was the most influential factor, followed by altitude and least by genotype. Aldehydes and alcohols correlated positively (r = 0.789; p &lt; 0.001), both accumulated in immature carobs and decreased with progressive ripening, resulting in the attenuation of green grassy aroma. Conversely, acids increased with ripening and dominated the carob volatilome at full maturity, correlating negatively with aldehydes and alcohols (r = −0.835 and r = −0.950, respectively; p &lt; 0.001). The most abundant VOC throughout ripening (17.3-57.7%) was isobutyric acid, responsible for the characteristic cheesy-acidic-buttery aroma of carob powder. The pleasurable aroma detected at the immature stages (RS2 and RS3) was traced to isobutyrate and methyl isobutyrate esters, rendering unripe green carob powder a potential admixture component for improving the aroma of novel food products. Lower altitude favored the accumulation of acids linked to less pleasant aroma, whereas isobutyric acid was more abundant at higher altitude. This constitutes a significant indication that higher altitude enhances the characteristic carob-like aroma and sensory quality of carob powder.

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

Integrated metabolic and microbial analysis reveals host–microbial interactions in IgE-mediated childhood asthma

A metabolomics-based approach to address the molecular mechanism of childhood asthma with immunoglobulin E (IgE) or allergen sensitization related to microbiome in the airways remains lacking. Fifty-three children with lowly sensitized non-atopic asthma (n = 15), highly sensitized atopic asthma (n = 13), and healthy controls (n = 25) were enrolled. Blood metabolomic analysis with 1H-nuclear magnetic resonance (NMR) spectroscopy and airway microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen-specific IgE levels for lowly and highly sensitized asthma was also assessed. Four metabolites including tyrosine, isovalerate, glycine, and histidine were uniquely associated with lowly sensitized asthma, whereas one metabolite, acetic acid, was strongly associated with highly sensitized asthma. Metabolites associated with highly sensitized asthma (valine, isobutyric acid, and acetic acid) and lowly sensitized asthma (isovalerate, tyrosine, and histidine) were strongly correlated each other (P < 0.01). Highly sensitized asthma associated metabolites were mainly enriched in pyruvate and acetyl-CoA metabolisms. Metabolites associated with highly sensitized atopic asthma were mostly correlated with microbiota in the airways. Acetic acid, a short-chain fatty acid (SCFA), was negatively correlated with the genus Atopobium (P < 0.01), but positively correlated with the genus Fusobacterium (P < 0.05). In conclusion, metabolomics reveals microbes-related metabolic pathways associated with IgE responses to house dust mite allergens in childhood asthma. A strong correlation of metabolites related to highly sensitized atopic asthma with airway microbiota provides linkages between the host–microbial interactions and asthma endotypes.

514 Late-Breaking: Effects of Feeding a High Canola Meal-containing Diet and Multi-carbohydrase Supplementation on Growth Performance and Intestinal Ecology of Piglets

The objective was to investigate the effects of a high canola meal-containing diet and multi-carbohydrase supplementation on growth performance and intestinal pH, short-chain fatty acid (SCFA) profile, and microbiome in weaned piglets. Twenty-four piglets (7.46 ± 0.23 kg BW) were individually assigned to 1 of 3 diets in a completely randomized design. Diets were fed for 21 d: SB, corn and soybean meal-based diet; CM, 25% canola meal substituting soybean meal and adjusted to meet energy and nutrient requirements of piglets (NRC, 2012); and CM+E, CM supplemented with multi-carbohydrase (0.01%). Feed disappearance and BW were recorded weekly. On d 21, piglets were euthanized to assess digesta pH, SCFA profile, and gut microbiome. Data were analyzed using the MIXED procedure of SAS using the piglet as the experimental unit. There were no differences (P &gt; 0.10) in growth performance and digesta pH. Piglets fed CM+E tended to (P = 0.051) or had significantly lower (P &lt; 0.05) butyric acid in the cecum than piglets fed CM and SB, respectively. Piglets fed SB had higher (P &lt; 0.05) isobutyric acid in the colon than piglets fed CM+E. Piglets fed SB and CM tended to have higher (P &lt; 0.05) isovaleric acid in the colon than piglets fed CM+E. Piglets fed SB tended to have lower (P &lt; 0.10) proportion of Bifidobacteria, and had lower (P &lt; 0.05) Enterobacteriaceae, Enterococcus, and Lactobacillus than piglets fed CM. Piglets fed CM+E tended to have lower (P &lt; 0.10) Bifidobacteria and higher Clostridium XIVa than piglets fed CM, and had lower (P &lt; 0.05) Enterococcus, but higher (P &lt; 0.05) Lactobacillus than piglets fed CM. In conclusion, feeding 25% of canola meal in substitution to soybean meal with or without multi-carbohydrase supplementation changed the intestinal environment by modifying SCFA profile and relative proportion of microbiome, but without affecting digesta pH or growth performance in nursery piglets.

Effects of Purple Corn Anthocyanin on Blood Biochemical Indexes, Ruminal Fluid Fermentation, and Rumen Microbiota in Goats

The objective of this study was to observe the effects of anthocyanin from purple corn on blood biochemical indexes, ruminal fluid fermentation parameters, and the microbial population in goats. A total of 18 Qianbei Ma wether kids (body weight, 21.38 ± 1.61 kg; mean ± standard deviation) were randomly assigned to three groups using a completely randomized design. The group diets were: (1) control, basal diet, (2) treatment 1 (LA), basal diet with 0.5-g/d purple corn pigment (PCP), and (3) treatment 2 (HA), basal diet with 1-g/d PCP. The results showed that supplementation of PCP anthocyanin increased (P &lt; 0.05) crude protein and gross energy digestibilities compared to the control. Compared to the control group, the inclusion of anthocyanin-rich PCP led to significantly increased (P &lt; 0.05) plasma reduced glutathione and peroxidase concentrations. Goats receiving PCP had increased (P &lt; 0.05) ruminal fluid acetic acid and a higher ratio of acetate to propionate, while the propionic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid levels had decreased (P &lt; 0.05). There was no significant difference (P &gt; 0.05) in ruminal fluid alpha bacterial diversity among the three groups. At the phylum level, the feeding of PCP had significant effect (P &lt; 0.05) on the abundances of Actinobacteriota, Proteobacteria, Elusimicrobiota, WPS-2, and Cyanobacteria. At the genus level, HA group had lower (P &lt; 0.05) Prevotellaceae_NK3B31_group abundance compared to the other groups. In addition, significant differences (P &lt; 0.05) were also observed for the ruminal fluid Eubacterium_nodatum_group, Amnipila, Ruminiclostridium, U29-B03, unclassified_c_Clostridia, Pyramidobacter, Anaeroplasma, UCG-004, Atopobium, norank_f_norank_o_Bradymonadales, Elusimicrobium, norank_f_norank_o_norank_c_norank_p_WPS-2, norank_f_Bacteroidales_UCG-001, and norank_f_norank_o_Gastranaerophilales among all groups. Taken together, the inclusion of anthocyanin-rich PCP increased the antioxidant potential, improved rumen volatile fatty acids, and induced a shift in the structure and relative abundance of ruminal microbiota in growing goats.

Effects of Dietary Supplementation of Lactobacillus delbrueckii on Gut Microbiome and Intestinal Morphology in Weaned Piglets

Lactobacillus delbrueckii is a Gram-positive bacterium mostly used in the dairy industry for yogurt and cheese. The present study was designed to evaluate the effects of Lactobacillus delbrueckii on serum biochemical parameters, intestinal morphology, and performance by supplementing at a dietary level of 0.1% in diets for weaned piglets. Eighty healthy weaned piglets (initial body weight: 7.56 ± 0.2 kg) were randomly divided into two feeding groups with four replicates in each group (n = 10 animals per replicate); piglets were fed with basal diet (CON) or basal diet containing 0.1% Lactobacillus delbrueckii (LAC). The results showed that dietary supplementation of Lactobacillus delbrueckii improved growth performance and increased serum HDL and insulin levels in piglets on the 28th day of the experimental time (p &lt; 0.05). The gut microbe analysis revealed that Lactobacillus delbrueckii significantly decreased the relative abundance of the phyla Bacteroidetes, but increased the relative abundance of the phyla Firmicutes. The Lactobacillus delbrueckii also significantly increased the relative abundance of Bifidobacterium and Lactobacillus at the genus level of the bacterial community in the ileum, but decreased the relative abundance of unclassified Clostridiales. Moreover, Lactobacillus delbrueckii improved mucosal morphology by obtaining higher intestinal villus height (p &lt; 0.05), significantly increasing the concentrations of butyrate, isobutyric acid, and isovaleric acid in colonic chyme of piglets, but decreasing the intestinal pH at the duodenum and ileum on the 28th day of the experimental time. In conclusion, dietary supplementation of Lactobacillus delbrueckii in the diet of weaned piglets can improve intestinal morphology and modulate the microbiota community to promote growth performance.

Data-Driven Strain Design Using Aggregated Adaptive Laboratory Evolution Mutational Data

Microbes are being engineered for an increasingly large and diverse set of applications. However, the designing of microbial genomes remains challenging due to the general complexity of biological system. Adaptive Laboratory Evolution (ALE) leverages nature's problem-solving processes to generate optimized genotypes currently inaccessible to rational methods. The large amount of public ALE data now represents a new opportunity for data-driven strain design. This study presents a novel and first of its kind meta-analysis workflow to derive data-driven strain designs from aggregate ALE mutational data using rich mutation annotations, statistical and structural biology methods. The mutational dataset consolidated and utilized in this study contained 63 Escherichia coli K-12 MG1655 based ALE experiments, described by 93 unique environmental conditions, 357 independent evolutions, and 13,957 observed mutations. High-level trends across the entire dataset were established and revealed that ALE-derived strain designs will largely be gene-centric, as opposed to non-coding, and a relatively small number of variants (approx. 4) can significantly alter cellular states and provide benefits which range from an increase in fitness to a complete necessity for survival. Three novel experimentally validated designs relevant to metabolic engineering applications are presented as use cases for the workflow. Specifically, these designs increased growth rates with glycerol as a carbon source through a point mutation to glpK and a truncation to cyaA or increased tolerance to toxic levels of isobutyric acid through a pykF truncation. These results demonstrate how strain designs can be extracted from aggregated ALE data to enhance strain design efforts.

Effect of Dietary Amylose/Amylopectin Ratio on Intestinal Health and Cecal Microbes’ Profiles of Weaned Pigs Undergoing Feed Transition or Challenged With Escherichia coli Lipopolysaccharide

BackgroundDietary amylose/amylopectin ratio (DAR) plays an important role in piglets’ intestinal health. It is controversial whether diarrhea could be relieved by changing DAR in weaning piglets.MethodsSixty (Landrace × Yorkshire) castrated male pigs (initial body weight (BW) 6.51 ± 0.64 kg) were randomly allocated to five groups (one pig per cage and 12 replicates per group) according to their BW. Piglets received diets with different DARs (0.00, 0.20, 0.40, 0.60, and 0.80) for 29 days. Feed transition occurs at day 15. The piglets were challenged with lipopolysaccharides (Escherichia coli LPS, 100 μg/kg BW) on day 29 by intraperitoneal injection at 12 h before slaughter. Chyme was collected for pH value, short-chain fatty acid (SCFA), and cecal microbe analysis using 16S rRNA gene sequencing; mucosa was sampled for detecting gene expression.ResultsRate and degree of diarrhea were higher when DAR was 0.40 than when it was 0.20 and 0.80 during the third week (P &lt; 0.05). The chyme pH value in the cecum was higher (P &lt; 0.05) in 0.20 DAR than in 0.00 and 0.80 DARs, but with no significant difference compared with 0.40 and 0.60 DARs (P &gt; 0.05). Cecal isobutyric acid and isovaleric acid concentrations were higher in 0.20 than in other groups (P &lt; 0.01). Cecal SCFAs such as acetic acid, propionic acid, and total SCFA, concentrations were higher in 0.40 DAR than in 0.00, 0.60, and 0.80 DARs (P &lt; 0.05), but with no significant difference when compared with 0.20 (P &gt; 0.05). Cecal crypt depth was lower (P &lt; 0.05) in 0.80 than in other groups, but not 0.40. Claudin mRNA expression in the mucosa of the ileum was higher in 0.20 than in other groups (P &lt; 0.01). The alpha diversity of cecal microbe representative by goods coverage was higher in group 0.40 when compared with group 0.20 (P &lt; 0.05). At the genus level, the abundances of the Ruminococcaceae_NK4A214_group and Anaerotruncus were higher but that of Cetobacterium was lower in the cecal chyme of group 0.20 than that of group 0.60 (P &lt; 0.05), with no significant difference compared with other groups (P &gt; 0.05). The diarrhea rate during the third week was negatively correlated with the abundances of Rikenellaceae_RC9_gut_group and X.Eubacterium_coprostanoligenes_group (P &lt; 0.05).ConclusionCompared with diet high in amylose or amylopectin, diet with DAR 0.40 showed a worse degree of diarrhea in weaned piglets during feed transition. But the intestinal health will be improved the week after the microbes and metabolites are regulated by DAR.

Synthesis and crystal structure of a one-dimensional chain-like strontium(II) coordination polymer built of N-methyldiethanolamine and isobutyrate ligands

The one-dimensional coordination polymer (I) [Sr(ib)2(H2mda)] n (Hib = isobutyric acid, C4H8O2, and H2mda = N-methyldiethanolamine, C5H13NO2), namely, catena-poly[[(N-methyldiethanolamine-κ3 O,N,O′)strontium(II)]-di-μ2-isobutyrato-κ3 O,O′:O;κ3 O:O,O′], was prepared by the one-pot aerobic reaction of [Zr6O4(OH)4(ib)12(H2O)]·3Hib with Sr(NO3)2 and H2mda in the presence of MnCl2 and Et3N in acetonitrile. The use of MnCl2 is key to the isolation of I as high-quality colorless crystals in good yield. The molecular solid-state structure of I was determined by single-crystal X-ray diffraction. Compound I crystallizes in the monoclinic space group P21/c and shows a one-dimensional polymeric chain structure. Each monomeric unit of this coordination polymer consists of a central SrII ion in the NO8 coordination environment of two deprotonated ib− ligands and one fully protonated H2mda ligand. The C and O atoms of the H2mda ligand were refined as disordered over two sets of sites with site occupancies of 0.619 (3) and 0.381 (3). Compound I shows thermal stability up to 130°C in air.