Gut Microbial Activity Research Articles

Chronic Strongyloides stercoralis infection increases presence of the Ruminococcus torques group in the gut and alters the microbial proteome

We explored the impact of chronic Strongyloides stercoralis infection on the gut microbiome and microbial activity in a longitudinal study. At baseline (time-point T0), 42 fecal samples from matched individuals (21 positive for strongyloidiasis and 21 negative) were subjected to microbiome 16S-rRNA sequencing. Those positive at T0 (untreated then because of COVID19 lockdowns) were retested one year later (T1). Persistent infection in these individuals indicated chronic strongyloidiasis: they were treated with ivermectin and retested four months later (T2). Fecal samples at T1 and T2 were subjected to 16S-rRNA sequencing and LC–MS/MS to determine microbial diversity and proteomes. No significant alteration of indices of gut microbial diversity was found in chronic strongyloidiasis. However, the Ruminococcus torques group was highly over-represented in chronic infection. Metaproteome data revealed enrichment of Ruminococcus torques mucin-degrader enzymes in infection, possibly influencing the ability of the host to expel parasites. Metaproteomics indicated an increase in carbohydrate metabolism and Bacteroidaceae accounted for this change in chronic infection. STITCH interaction networks explored highly expressed microbial proteins before treatment and short-chain fatty acids involved in the synthesis of acetate. In conclusion, our data indicate that chronic S. stercoralis infection increases Ruminococcus torques group and alters the microbial proteome.

Gut microbial metabolism of 5-ASA diminishes its clinical efficacy in inflammatory bowel disease.

For decades, variability in clinical efficacy of the widely used inflammatory bowel disease (IBD) drug 5-aminosalicylic acid (5-ASA) has been attributed, in part, to its acetylation and inactivation by gut microbes. Identification of the responsible microbes and enzyme(s), however, has proved elusive. To uncover the source of this metabolism, we developed a multi-omics workflow combining gut microbiome metagenomics, metatranscriptomics and metabolomics from the longitudinal IBDMDB cohort of 132 controls and patients with IBD. This associated 12 previously uncharacterized microbial acetyltransferases with 5-ASA inactivation, belonging to two protein superfamilies: thiolases and acyl-CoA N-acyltransferases. In vitro characterization of representatives from both families confirmed the ability of these enzymes to acetylate 5-ASA. A cross-sectional analysis within the discovery cohort and subsequent prospective validation within the independent SPARC IBD cohort (n = 208) found three of these microbial thiolases and one acyl-CoA N-acyltransferase to be epidemiologically associated with an increased risk of treatment failure among 5-ASA users. Together, these data address a longstanding challenge in IBD management, outline a method for the discovery of previously uncharacterized gut microbial activities and advance the possibility of microbiome-based personalized medicine.

Mangiferin alleviates trimethylamine-N-oxide (TMAO)-induced atherogenesis and modulates gut microbiota in mice.

Trimethylamine-N-oxide (TMAO), originating from dietary trimethylamine-containing nutrients such as choline, has been recognized as a risk factor for atherosclerosis. Mangiferin is a bioactive xanthone initially extracted from mango (Mangifera indica). The present study aimed to investigate the effect of mangiferin on TMAO-induced atherogenesis in mice fed a high-choline diet. Female ApoE-/- mice were randomly divided into three groups and fed either a control diet, a high-choline diet with 1% free choline, or an experimental diet with 1% free choline plus 0.5% mangiferin for 15 weeks. Our results showed that a high-choline diet elevated plasma TMAO levels, accelerated atherogenesis, promoted cholesterol accumulation, and reduced the generation of short-chain fatty acids (SCFAs) by gut microbes. Mangiferin alleviated inflammation, and lowered plasma total cholesterol levels by facilitating the elimination of neutral and acidic sterols in feces, resulting in a 16.7-29.0% reduction in aortic atherosclerotic lesions. Notably, mangiferin could favorably remodel the composition of the gut microbiota by fostering the growth of the beneficial taxa Akkermansia, Parabacteroides, and Bifidobacteriaceae, while reducing the relative abundance of the pathogenic genus Helicobacter. This modulation led to a decrease in plasma lipopolysaccharide levels, enhanced the production of total SCFAs by gut microbes, and reduced susceptibility to atherosclerosis. In conclusion, mangiferin exhibited its ability to alleviate TMAO-induced atherosclerosis through its anti-inflammatory, cholesterol-lowering, and gut microbial modulatory activities.

Bile acids and microbes in metabolic disease

Bile acids (BAs) serve as physiological detergents that enable the intestinal absorption and transportation of nutrients, lipids and vitamins. BAs are primarily produced by humans to catabolize cholesterol and play crucial roles in gut metabolism, microbiota habitat regulation and cell signaling. BA-activated nuclear receptors regulate the enterohepatic circulation of BAs which play a role in energy, lipid, glucose, and drug metabolism. The gut microbiota plays an essential role in the biotransformation of BAs and regulates BAs composition and metabolism. Therefore, altered gut microbial and BAs activity can affect human metabolism and thus result in the alteration of metabolic pathways and the occurrence of metabolic diseases/syndromes, such as diabetes mellitus, obesity/hypercholesterolemia, and cardiovascular diseases. BAs and their metabolites are used to treat altered gut microbiota and metabolic diseases. This review explores the increasing body of evidence that links alterations of gut microbial activity and BAs with the pathogenesis of metabolic diseases. Moreover, we summarize existing research on gut microbes and BAs in relation to intracellular pathways pertinent to metabolic disorders. Finally, we discuss how therapeutic interventions using BAs can facilitate microbiome functioning and ease metabolic diseases.

Differences in gut microbial fructoselysine degradation activity between breast-fed and formula-fed infants.

The Amadori product fructoselysine is formed upon heating of food products and is abundantly present in infant formula while being almost absent in breast milk. The human gut microbiota can degrade fructoselysine for which interindividual differences have been described for adults. The aim of this study is to compare functional differences in microbial fructoselysine degradation between breast-fed and formula-fed infants, in view of their different diets and resulting different fructoselysine exposures. First, a publicly available metagenomic dataset with metagenome-assembled genomes (MAGs) from infant fecal samples was analyzed and showed that query genes involved in fructoselysine degradation (frlD/yhfQ) were abundantly present in multiple bacterial taxa in the fecal samples, with a higher prevalence in the formula-fed infants. Next, fecal samples collected from exclusively breast-fed and formula-fed infants were anaerobically incubated with fructoselysine. Both groups degraded fructoselysine, however the fructoselysine degradation activity was significantly higher by fecal samples from formula-fed infants. Overall, this study provides evidence that infant formula feeding, leading to increased dietary fructoselysine exposure, seems to result in an increased fructoselysine degradation activity in the gut microbiota of infants. This indicates that the infant gut microbiota adapts towards dietary fructoselysine exposure.

Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes.

Type 1 diabetes mellitus is characterized with decreased microbial diversity. Gut microbiota is essential for the normal physiological functioning of many organs, especially the brain. Prebiotics are selectively fermentable oligosaccharides [xylooligosaccharides (XOS), galactooligosaccharides, etc.] that promote the growth and activity of gut microbes and influence the gut-brain axis. Aerobic exercise is a non-pharmacological approach for the control of diabetes and could improve cognitive functions. The potential beneficial effect of XOS and/or aerobic training on cognition, the lipid profile and oxidative stress markers of experimental rats were evaluated in this study. Male Wistar rats were randomly divided into three streptozotocin-induced diabetic groups and a control group. Some of the rats, either on a XOS treatment or a standard diet, underwent aerobic training. The results showed that the aerobic training independently lowered the total cholesterol levels compared to the sedentary diabetic rats (p = 0.032), while XOS lowers the malondialdehyde levels in the trained diabetic rats (p = 0.034). What is more the exercise, independently or in combination with XOS beneficially affected all parameters of the behavioral tests. We conclude that aerobic exercises alone or in a combination with the prebiotic XOS could ameliorate the dyslipidemia, oxidative stress, and cognitive abilities in experimental type 1 diabetic animals.

The Intake of Antioxidant Capacity of Children Depends on Their Health Status.

The gastrointestinal digestion of food and further gut microbial activity render a myriad of different molecules that could be responsible for the biological activities that are classically assigned to their parent compounds. This has been previously shown for some phytochemicals whose antioxidant capacity was either increased or decreased after being metabolized by gut microbes. Whether a global antioxidant capacity that is extracted from food is determined by the gut microbial community structure is still not well described. In the present study, we in vitro digested and fermented 48 different foods that were submitted to different culinary treatments using the stools of lean children, obese children, celiac children and children with an allergy to cow’s milk proteins. Their antioxidant capacities were assessed with the DPPH and FRAP assays, and the percentage that each food contributed to their daily antioxidant intake as well as their antioxidant capacity by portion size was inferred. Overall, cereals, fruits and vegetables displayed a higher contribution to their daily antioxidant intake, while tubers, fish and meat exhibited a higher antioxidant capacity by serving size. The food that was fermented in the lean children’s and those children that were allergic to cow’s milk protein’s fecal material, showed a higher antioxidant capacity, which could imply that there is a larger role of the gut microbiota in this area.

The Important Role of TaohongSiwu Decoction in Gut Microbial Modulation in Response to High-Salt Diet-Induced Hypertensive Mice

TaohongSiwu decoction (THSWD), a traditional Chinese recipe, has been widely used to treat hypertension since ancient times. However, the mechanisms of its action are still unclear. Herein, we aimed to explore the gut microbial activity of THSWD in high-salt diet-induced hypertensive mice. Eight percent high-salt (NaCl) diet was used to induce hypertension for 4 weeks in a mouse model. Meanwhile, THSWD was used to intervene in the high-salt diet-induced mice, and the efficacy was evaluated by different parameters. Here, we found that THSWD significantly restored blood pressure compared with the model group. Moreover, THSWD effectively protected endothelial function by significantly upregulating the level of nitric oxide (NO) and downregulating the level of endothelin-1 (ET-1), angiotensin I (AngI), and vascular endothelial growth factor (VEGF) in serum compared with the model group. Notably, THSWD significantly upregulated the relative abundance of Dubosiella and downregulated that of Cyanobium_PCC-6307 and DNF00809 at the genus level compared with the model group. The results of PCA and microbial distance calculation further exhibited that THSWD treatment resulted in significant regulation of the microbial community. Furthermore, compared with the model group, THSWD increased the level of vitamin k2 (VK2) in serum. These findings indicate that THSWD could protect blood pressure and endothelial function by regulating gut microbiota and promoting microbial metabolite VK2. These results show the important role of THSWD in regulating the gut microbiota in response to high-salt diet-induced mice.

Organelle 16S rRNA amplicon sequencing enables profiling of active gut microbiota in murine model.

High-throughput sequencing of ribosomal RNA (rRNA) amplicons has served as a cornerstone in microbiome studies. Despite crucial implication of organelle 16S rRNA measurements to host gut microbial activities, genomic DNA (gDNA) was overwhelmingly targeted for amplicon sequencings. Although gDNA could be a reliable resource for gene existing validation, little information is revealed in regard to the activity of microorganisms owing to the limited changes gDNA undertaken in inactive, dormant, and dead bacteria. We applied both rRNA- and gDNA-derived sequencings on mouse cecal contents. Respective experimental designs were verified to be suitable for nucleic acid (NA) purification. Via benchmarking, mainstream 16S rRNA hypervariable region targets and reference databases were proven adequate for respective amplicon sequencing study. In phylogenetic studies, significant microbial composition differences were observed between two methods. Desulfovibrio spp. (an important group of anaerobic gut microorganisms that has caused analytical difficulties), Pediococcus spp., and Proteobacteria were drastically lower as represented by gDNA-derived compositions, while microbes like Firmicutes were higher as represented by gDNA-derived microbiome compositions. Also, using PICRUSt2 as an example, we illustrated that rRNA-derived sequencing might be more suitable for microbiome function predictions since pathways like sugar metabolism were lower as represented by rRNA-derived results. The findings of this study demonstrated that rRNA-derived amplicon sequencing could improve identification capability of specific gut microorganisms and might be more suitable for in silico microbiome function predictions. Therefore, rRNA-derived amplicon sequencings, preferably coupled with gDNA-derived ones, could be used as a capable tool to unveil active microbial components in host gut. KEY POINTS: •Conventional pipelines were adequate for the respective amplicon sequencing study •Groups, such as Desulfovibrio spp., were differently represented by two methods •Comparative amplicon sequencings could be useful in host active microbiota studies.

Butyrate to combat obesity and obesity-associated metabolic disorders: Current status and future implications for therapeutic use.

SummaryEvidence is increasing that disturbances in the gut microbiome may play a significant role in the etiology of obesity and type 2 diabetes. The short chain fatty acid butyrate, a major end product of the bacterial fermentation of indigestible carbohydrates, is reputed to have anti‐inflammatory properties and positive effects on body weight control and insulin sensitivity. However, whether butyrate has therapeutic potential for the treatment and prevention of obesity and obesity‐related complications remains to be elucidated. Overall, animal studies strongly indicate that butyrate administered via various routes (e.g., orally) positively affects adipose tissue metabolism and functioning, energy and substrate metabolism, systemic and tissue‐specific inflammation, and insulin sensitivity and body weight control. A limited number of human studies demonstrated interindividual differences in clinical effectiveness suggesting that outcomes may depend on the metabolic, microbial, and lifestyle‐related characteristics of the target population. Hence, despite abundant evidence from animal data, support of human data is urgently required for the implementation of evidence‐based oral and gut‐derived butyrate interventions. To increase the efficacy of butyrate‐focused interventions, future research should investigate which factors impact treatment outcomes including baseline gut microbial activity and functionality, thereby optimizing targeted‐interventions and identifying individuals that merit most from such interventions.

A Bifidogenic Prebiotic Supplement Beneficially Alters Gut Microbial Composition, Activity, and Plasma Metabolites in Healthy Individuals Consuming Low Fiber Diets

A randomized order, double‐blinded, placebo‐controlled cross‐over intervention study was conducted to test the effectiveness of a prebiotic supplement in healthy participants consuming a diet low in fiber. This clinical trial was registered at clinicaltrials.gov as NCT03785860.Fecal microbial DNA was extracted and sequenced with shallow shotgun sequencing for metagenomics. Plasma metabolites were analyzed with untargeted liquid chromatography–mass spectrometry for metabolomics. Statistical analyses were performed with the package edgeR in R version 4.0.2. For each outcome, linear mixed models were used with fixed effects of treatment, treatment order, and their interaction and random effect of individual participants.From the metagenomic analysis, the relative abundance of the genus Bifidobacterium and several bifidobacterial species increased after prebiotic supplementation compared to the placebo. Additionally, gene counts of genes sacA, xfp, xpk associated with prebiotic utilization significantly increased after the prebiotic supplement. Other genes that increased in counts were poxB and ackA, which are related to acetate metabolism. Changes in bifidobacteria abundance were positively correlated with changes in genes related to fructose and choline metabolism, and negatively correlated with a gene that encodes for acetate kinase.Plasma concentrations of indolepropionate significantly increased whereas choline and several acylcholines such as stearoylcholine, dihomo‐linolenoyl‐choline, linoleoylcholine, arachidonoylcholine, palmitoylcholine, and oleoylcholine significantly decreased after the prebiotic compared to the placebo arm.The results of this study demonstrate that a convenient, easy to use bifidogenic prebiotic supplement beneficially altered gut microbial composition and activity, which was reflected in changes in plasma metabolites in healthy individuals consuming low fiber diets.

Insecticidal and growth inhibitory activity of gut microbes isolated from adults of Spodoptera litura (Fab.)

BackgroundSpodoptera litura (Fab.) (Lepidoptera: Noctuidae) commonly known as tobacco caterpillar is a polyphagous pest that causes significant damage to many agricultural crops. The extensive use of chemical insecticides against S. litura has resulted in development of resistance. In order to find potential biocontrol agents, gut microbes were investigated for insecticidal potential. These microbes live in a diverse relationship with insects that may vary from beneficial to pathogenic.ResultsEnterococcus casseliflavus, Enterococcus mundtii, Serratia marcescens, Klebsiella pneumoniae, Pseudomonas paralactis and Pantoea brenneri were isolated from adults of S. litura. Screening of these microbial isolates for insecticidal potential against S. litura showed higher larval mortality due to K. pneumoniae and P. paralactis. These bacteria also negatively affected the development of insect along with significant decline in relative growth and consumption rate as well as efficiency of conversion of ingested and digested food of insect. The bacteria significantly decreased the reproductive potential of insect. Perturbations in the composition of gut microbiome and damage to gut epithelium were also observed that might be associated with decreased survival of this insect.ConclusionsOur study reveals the toxic effects of K. pneumoniae and P. paralactis on biology of S. litura. These bacteria may be used as potential candidates for developing ecofriendly strategies to manage this insect pest.

Abstract P077: Midlife Physical Activity Is Associated With Gut Microbial Species And Metabolic Pathways: Coronary Artery Risk Development In Young Adults Study

Background: Behavioral factors for cardiometabolic outcomes have been shown to influence the composition and function of the gut microbiota, which has been associated with cardiometabolic outcomes. Observational studies have documented associations between physical activity and gut microbial composition using 16S rRNA sequencing data, but there is a paucity of data on functional measures, which can be generated from whole-metagenomics sequencing (WMS). Methods: Data are from 480 CARDIA participants who attended the Year 30 follow-up exam (2015-2016, ages 48-60, 47:53 Black:White race, 47:53 male:female gender). Physical activity (exercise units) was estimated from reported frequency and duration of 13 activity types of at least moderate intensity during the previous year. Species, metabolic pathways, and enzyme families were assigned using standard reference databases. Multivariate measures of beta-diversity (between-person) was assessed with principal coordinates analysis (PCoA) and tested with PERMANOVA. Multivariable-adjusted linear regression was used to test associations between distinct microbial features and physical activity, adjusting for false discovery rate (FDR). Results: Sequence data mapped to 105 species 1,307 enzyme families, and 318 metabolic pathways. Beta-diversity of species, but not for enzyme families or metabolic pathways, was significantly differentiated according to physical activity. In analysis of distinct microbial features, 7 species, 15 enzyme families, and 3 metabolic pathways were significantly associated with physical activity at an FDR-adjusted p-value of 0.10 (Table). Conclusion: These findings support associations between gut microbial features and physical activity in a middle-aged, bi-race population-based cohort. Although temporality cannot be established from these cross-sectional analyses, our results are consistent with data suggesting that physical activity may influence composition and function of the gut microbiota.

Evaluation of the Effect of Food Products Containing Prebiotics and Bacillus subtilis HU58 on the Gut Microbial Community Activity and Community Composition Using an In Vitro M-SHIME® Model

GoodBiome™ Foods is a collection of foods infused with prebiotics, including inulin and xylooligosaccharides, and the probiotic Bacillus subtilis HU58. The effects of repeated intake of three predigested GoodBiome™ Foods products and one comparator product on microbial community activity and composition were assessed using the mucosal simulator of the human intestinal microbial system (M-SHIME®) platform with proximal colon (PC) and distal colon (DC) compartments and conducted under healthy gut conditions. Treatment with all test products increased short-chain fatty acid (SCFA) production (acetate, propionate, and butyrate) versus the control period in both the PC and DC. The highest increases were seen with the GoodBiome™ Foods products. Ammonium and branched SCFA levels were also increased (versus the control period) in both compartments. Treatment with all test products enhanced the Simpson diversity index (versus the control period), reaching significance for all test products in the PC (p < 0.05). Treatment with all test products resulted in changes in the microbial community composition. The relative abundance increased for Proteobacteria and decreased for Actinobacteria in the PC and DC. Repeated intake of GoodBiome™ Food products increased SCFA production and microbial diversity in an M-SHIME® model of the human intestinal microbiome.

SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice.

Increased protease activity has been linked to the pathogenesis of IBD. While most studies have been focusing on host proteases in gut inflammation, it remains unclear how to address the potential contribution of their bacterial counterparts. In the present study, we report a functional characterization of a newly identified serine protease, SP-1, from the human gut microbiota. The serine protease repertoire of gut Clostridium was first explored, and the specificity of SP-1 was analyzed using a combinatorial chemistry method. Combining in vitro analyses and a mouse model of colitis, we show that oral administration of recombinant bacteria secreting SP-1 (i) compromises the epithelial barrier, (ii) alters the microbial community, and (ii) exacerbates colitis. These findings suggest that gut microbial protease activity may constitute a valuable contributor to IBD and could, therefore, represent a promising target for the treatment of the disease.

Interactions between dietary fibre and the gut microbiota.

Research characterising the gut microbiota in different populations and diseases has mushroomed since the advent of next-generation sequencing techniques. However, there has been less emphasis on the impact of dietary fibres and other dietary components that influence gut microbial metabolic activities. Dietary fibres are the main energy source for gut bacteria. However, fibres differ in their physicochemical properties, their effects on the gut and their fermentation characteristics. The diversity of carbohydrates and associated molecules in fibre-rich foods can have a major influence on microbiota composition and production of bioactive molecules, for example SCFAs and phenolic acids. Several of these microbial metabolites may influence the functions of body systems including the gut, liver, adipose tissues and brain. Dietary fibre intake recommendations have recently been increased (to 30 g daily) in response to growing obesity and other health concerns. Increasing intakes of specific fibre and plant food sources may differentially influence the bacteria and their metabolism. However, in vitro studies show great individual variability in the response of the gut microbiota to different fibres and fibre combinations, making it difficult to predict which foods or food components will have the greatest impact on levels of bioactive molecules produced in the colon of individuals. Greater understanding of individual responses to manipulation of the diet, in relation to microbiome composition and production of metabolites with proven beneficial impact on body systems, would allow the personalised approach needed to best promote good health.

Effect of carcass contamination on necrophagous invertebrate performance

BackgroundThe breakdown of dead organic matter is driven by a diverse array of organisms and is an important process increasingly impacted by a range of contaminants. While many studies have documented how contaminants affect food webs that are fueled by decaying plant litters, much less is known about how contaminants affect organisms that rely on dead animal material. Here, we begin to explore the effects of food contamination—using silver nanoparticles (AgNPs) as a model contaminant—on the carrion beetle Nicrophorus vespilloides that buries carcasses of small vertebrates in soils as food source and larval nursing grounds.ResultsOur data show that a single ingestion of a non-lethal dose of 1 μg mL−1 AgNPs by adult female beetles does not affect overall gut microbial activity but results in shifts in the gut microbial community composition towards pathogens including Alcaligenes, Morganella, and Pseudomonas. While no effects were observed in offspring clutch size, some reductions were visible in clutch weight, number of larvae, and number of eclosing pupae in exposed N. vespilloides in comparison with controls. Repeated ingestion of AgNPs over several weeks led to a decrease in survival of adult beetles, suggesting that more environmentally realistic exposure scenarios can directly affect the success of carcass-feeding animals.ConclusionsSub-lethal carcass contamination with a model pollutant can affect the gut microbial composition in female beetles and reduce offspring fitness. This encourages consideration of currently overlooked propagation routes of contaminants through necrophagous food webs and inherent consequences for ecological and evolutionary processes.

Biodegradation of foam plastics by Zophobas atratus larvae (Coleoptera: Tenebrionidae) associated with changes of gut digestive enzymes activities and microbiome

In order to uncover the plastic types that superworm Zophobas atratus can degrade and the underlying changes associated with plastics consumption, three types of plastics including polystyrene (PS), polyethylene (PE) and polyurethane (PU) foam were used as sole feedstock to feed the superworm larvae for 35 days with bran as control. Compared to the control, PS- or PU-fed larvae showed 100% survival rates, the PE-fed and starvation larvae had decreased survival rates of 81.67% and 65%, respectively. Both plastics-fed and starvation groups showed decreased larvae weight. The consumption rates of PS, PE, and PU were 1.41, 0.30, and 0.74 mg/d/larva, respectively. The attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and differential scanning calorimeter and thermogravimetric (DSC-TGA) analyses demonstrated the changes of functional groups and thermostability in frass compared to plastic feedstocks, indicating the partial oxidation and degradation of plastics. Among the gut digestive enzymes tested, protease showed increased activities in all plastics-fed groups. Gut microbial communities displayed significant relative abundance changes such as increased abundances of Enterococcus in all plastic-fed groups, Citrobacter in PE-fed group, Dysgonomonas and Sphingobacterium in PS-fed group, and Mangrovibacter in PU-fed group. The latter 3 genera were reported for the first time. In summary, the results demonstrated that Z. atratus could efficiently degrade both PS and PU foam plastics, and the plastic degradation was associated with changes of gut microbial communities and digestive enzyme activities.

Postnatal development of gut microbial activity and their importance for jejunal motility in piglets.

Despite their anti-inflammatory properties, role in barrier function, absorption and microbial balance in the gut, knowledge on maturational and dietary effects on intestinal short-chain fatty acids (SCFA) in neonatal piglets is scarce. Moreover, little information exists whether SCFA and lactic acid (LA) modulates gut motility at this age. The present study aimed (1) to investigate the maturational changes in the SCFA profile with and without creep feeding of piglets in the first 3 wk of life; and (2) to examine the effects of SCFA and LA on muscle contractibility in jejunal tissue from neonatal piglets ex vivo. SCFA concentrations were measured in fecal samples of 52 piglets from 10 litters collected on days 2, 6, 13, and 20 of life using gas chromatography. Half of the litters were fed a commercial creep feed from day 10 of life. The organ bath system was used to test the effect of SCFA (acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, and caproate) as well as of LA and the combination of LA and SCFA on muscle contractibility in piglet's jejunum. Average daily gain of piglets was similar between groups before and after introduction of creep feed. SCFA were detectable in feces in relevant concentrations from day 2 of life and increased on day 6 in males by 3.0-fold and on day 13 in females by 1.6-fold but decreased again on day 20 in both sexes compared with day 2 (P < 0.05). Creep feeding reduced fecal SCFA by 0.6-fold on day 13 without largely modifying molar proportions, whereas it increased fecal SCFA by 0.8-fold on day 20 of life compared with the sow-reared only piglets (P < 0.05). Applying SCFA ex vivo increased the muscle contraction of the jejunum by 30% (P < 0.05). Likewise, addition of LA and the combination of LA and SCFA increased the jejunal muscle contractibility by 34.9% and 32.2%, respectively, compared with the muscle tension preaddition (P < 0.05). In conclusion, the present results for fecal SCFA in first days of life suggest high bacterial activity on milk components and emphasize the importance of SCFA for intestinal development and function. After a lag phase, creep feeding promotes fermentation in the distal colon, which may be beneficial for the gut homeostasis. Results further demonstrate the stimulating effect of SCFA and LA for jejunal motility, suggesting a role for mixing of digesta (segmentation) and digestion and absorption of nutrients as well as passage in the jejunum of neonatal piglets.

Impact of manipulation of glycerol/diol dehydratase activity on intestinal microbiota ecology and metabolism.

Glycerol/diol dehydratases (GDH) are enzymes that catalyse the production of propionate from 1,2-propanediol, and acrolein from glycerol. Acrolein reacts with dietary carcinogenic heterocyclic amines (HCA), reducing HCA mutagenicity, but is itself also an antimicrobial agent and toxicant. Gut microbial GDH activity has been suggested as an endogenous acrolein source; however, there is limited information on the potential of the intestinal microbiota to have GDH activity, and what impact it can have on the intestinal ecosystem and host health. We hypothesized that GDH activity of gut microbiota is determined by the abundance and distribution of GDH-active taxa and can be enhanced by supplementation of the GDH active Anaerobutyricum hallii, and tested this hypothesis combining quantitative profiling of gdh, model batch fermentations, microbiota manipulation, and kinetic modelling of acrolein formation. Our results suggest that GDH activity is a common trait of intestinal microbiota shared by a few taxa, which was dependent on overall gdh abundance. Anaerobutyricum hallii was identified as a key taxon in GDH metabolism, and its supplementation increased the rate of GDH activity and acrolein release, which enhanced the transformation of HCA and reduced fermentation activity. The findings of this first systematic study on acrolein release by intestinal microbiota indicate that dietary and microbial modulation might impact GDH activity, which may influence host health.