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Propionate as a health-promoting microbial metabolite in the human gut
Abstract
Propionate is a major microbial fermentation metabolite in the human gut with putative health effects that extend beyond the gut epithelium. Propionate is thought to lower lipogenesis, serum cholesterol levels, and carcinogenesis in other tissues. Steering microbial propionate production through diet could therefore be a potent strategy to increase health effects from microbial carbohydrate fermentation. The present review first discusses the two main propionate-production pathways and provides an extended gene-based list of microorganisms with the potential to produce propionate. Second, it evaluates the promising potential of arabinoxylan, polydextrose, and L-rhamnose to act as substrates to increase microbial propionate. Third, given the complexity of the gut microbiota, propionate production is approached from a microbial-ecological perspective that includes interaction processes such as cross-feeding mechanisms. Finally, it introduces the development of functional gene-based analytical tools to detect and characterize propionate-producing microorganisms in a complex community. The information in this review may be helpful for designing functional food strategies that aim to promote propionate-associated health benefits.
... regulating cholesterol production, which contributes to lowering the risk of cardiovascular disease. It also plays a significant role in supporting probiotic activity [36]. In this study, it was observed that both B. adolescentis and L. acidophilus produced SCFAs, primarily acetic acid and propionic acid. ...
... On the other hand, propionate plays a crucial role in regulating cholesterol production, which contributes to lowering the risk of cardiovascular disease. It also plays a significant role in supporting probiotic activity [36]. In this study, it was observed that both B. adolescentis and L. acidophilus produced SCFAs, primarily acetic acid and propionic acid. ...
... It is widely recognized that a symbiotic relationship exists between the intestinal microflora and the host, with a close association between the intestinal microflora and the pathogenesis of colitis [36]. In this study, the intestinal flora in colitis mice before and after administering the XOS solutions was analyzed using 16S rDNA amplifier sequencing. ...
Xylo-oligosaccharides (XOS) enriched with high fractions of X2-X3 are regarded as an effective prebiotic for regulating the intestinal microflora. In this study, the original XOS solution was obtained from bamboo shoots through hydrothermal pretreatment under optimized conditions. Subsequently, enzymatic hydrolysis with endo-xylanase was performed on the original XOS solution to enhance the abundance of the X2-X3 fractions. The results demonstrated that hydrothermal pretreatment yielded 21.24% of XOS in the hydrolysate solution, and subsequent enzymatic hydrolysis significantly increased the proportion of the X2-X3 fractions from 38.87% to 68.21%. Moreover, the XOS solutions with higher amounts of X2-X3 fractions exhibited superior performance in promoting the growth of probiotics such as Bifidobacterium adolescentis and Lactobacillus acidophilus in vitro, leading to increased production of short-chain fatty acids. In the in vivo colitis mouse model, XOS solutions with higher contents of X2-X3 fractions demonstrated enhanced efficacy against intestinal inflammation. Compared with the colitis mice (model group), the XOS solution with higher X2-X3 fractions (S1 group) could significantly increase the number of Streptomyces in the intestinal microflora, while the original XOS solution (S2 group) could significantly increase the number of Bacteroides in the intestinal microflora of colitis mice. In addition, the abundances of Alcaligenes and Pasteurella in the intestinal microflora of the S1 and S2 groups were much lower than in the model group. This effect was attributed to the ability of these XOS solutions to enhance species diversity, reversing the imbalance and disorder within the intestinal microflora. Overall, this work highlights the outstanding potential of XOS enriched with high contents of X2-X3 fractions as a regulator of the intestinal microbiota and as an anti-colitis agent.
... In general, easily fermentable compounds are fermented in the proximal colon where they promote SCFA production and increase lactic acid bacteria populations [208]. Acetate, propionate and butyrate are the main SCFA; they occur in molecular ratios of 60:20:20 in the colon [209]. These molecules regulate inflammatory response (depending on their concentration) and promote the regeneration of intestinal cells [57,210]. ...
... Damen et al. (2012) observed increased faecal total SCFA concentrations with a butyrate upsurge of 70% in healthy volunteers [223]. According to Van Craeyveld et al. (2008), the bifidogenic potency is influenced by AXOS DP [209]. Low DP is more efficient on bacteria proliferation. ...
Wheat bran (WB) consists mainly of different histological cell layers (pericarp, testa, hyaline layer and aleurone). WB contains large quantities of non-starch polysaccharides (NSP), including arabinoxylans (AX) and β-glucans. These dietary fibres have long been studied for their health effects on management and prevention of cardiovascular diseases, cholesterol, obesity, type-2 diabetes, and cancer. NSP benefits depend on their dose and molecular characteristics, including concentration, viscosity, molecular weight, and linked-polyphenols bioavailability. Given the positive health effects of WB, its incorporation in different food products is steadily increasing. However, the rheological, organoleptic and other problems associated with WB integration are numerous. Biological, physical, chemical and combined methods have been developed to optimise and modify NSP molecular characteristics. Most of these techniques aimed to potentially improve food processing, nutritional and health benefits. In this review, the physicochemical, molecular and functional properties of modified and unmodified WB are highlighted and explored. Up-to-date research findings from the clinical trials on mechanisms that WB have and their effects on health markers are critically reviewed. The review points out the lack of research using WB or purified WB fibre components in randomized, controlled clinical trials.
... Many beneficial effects induced by intestinal microbiota modulation are associated with SCFA production (Gómez et al., 2019). The approximate SCFA proportions in the large intestine are acetic acid (65%), propionic acid (25%), and butyric acid (15%) (Tingirikari, 2018), although acetic acid could be utilized by different microorganisms to produce propionic and butyric acids (Hosseini, Grootaert, Verstraete, & Van de Wiele, 2011;Riviere, Selak, Lantin, Leroy, & De Vuyst, 2016). The highest production of acetic acid occurred in media with FDBR and FDBSL, which is associated with cholesterol metabolism, lipogenesis, and hormonal appetite regulation in humans (Rowland et al., 2018). ...
... Considering the contents of the measured SCFA contents during colonic fermentation, there were far more propionic acid-producing bacteria in the tested fecal inoculum than those producing acetic and butyric acids, corroborating with the detected high relative abundance of Bacteroides spp./Prevotella spp. This indicates the predominance of Prevotella genus since Prevotella-dominant cultures produce substantially higher ratios of propionic acid to acetic and butyric acids than Bacteroides-dominant cultures (Hosseini et al., 2011;Sanders et al., 2019). However, propionic acid decreased overall in media with FDBR and FDBSL during colonic fermentation, agreeing with early studies showing that the presence of pectin causes a decrease in propionic acid during colonic fermentation (Bang et al., 2018;Ferreira-Lazarte, Kachrimanidou, Villamiel, Rastall, & Moreno, 2018;Yang, Martínez, Walter, Keshavarzian, & Rose, 2013). ...
This study investigated the effects of freeze-dried red beet root (FDBR) and freeze-dried red beet stem and leaves (FDBSL) on target bacterial groups and metabolic activity of human colonic microbiota in vitro. The capability of FDBR and FDBSL to cause alterations in the relative abundance of different selected bacterial groups found as part of human intestinal microbiota, as well as in pH values, sugar, short-chain fatty acid, phenolic compounds, and antioxidant capacity were evaluated during 48 h of in vitro colonic fermentation. FDBR and FDBSL were submitted to simulated gastrointestinal digestion and freeze-dried prior to use in colonic fermentation. FDBR and FDBSL overall increased the relative abundance of Lactobacillus spp./Enterococcus spp. (3.64 - 7.60%) and Bifidobacterium spp. (2.76 - 5.78%) and decreased the relative abundance of Bacteroides spp./Prevotella spp. (9.56 - 4.18%), Clostridium histolyticum (1.62 - 1.15%), and Eubacterium rectale/Clostridium coccoides (2.33 - 1.49%) during 48 h of colonic fermentation. FDBR and FDBSL had high positive prebiotic indexes (>3.61) during colonic fermentation, indicating selective stimulatory effects on beneficial intestinal bacterial groups. FDBR and FDBSL increased the metabolic activity of human colonic microbiota, evidenced by decreased pH, sugar consumption, short-chain fatty acid production, alterations in phenolic compound contents, and maintenance of high antioxidant capacity during colonic fermentation. The results indicate that FDBR and FDBSL could induce beneficial alterations in the composition and metabolic activity of human intestinal microbiota, as well as that conventional and unconventional red beet edible parts are candidates to use as novel and sustainable prebiotic ingredients.
... Certain bacterial species in the gut ferment indigestible dietary fibers into SCFAs, such as acetate, propionate, and butyrate, to mediate host energy balance, immune modulation, and mucosal barrier function (7,49,50). We do know that the gut microbial product butyrate upregulates the expression of tight junction proteins and induces the differentiation of Tregs in the colonic mucosa to maintain gut homeostasis (51). For instance, dietary fiber can prevent and treat intestinal inflammation induced by a high-carbohydrate and low-fiber western diet in mice by repairing the damaged intestinal mucus layer (29). ...
... Furthermore, the family Lachnospiraceae (which includes the genus Lachnospira), Roseburia, Oribacterium Lachnospiraceae_UCG-006, and Lachnospiraceae_XPB1014_group are known to be SCFA-producing bacteria (64). Lachnospira, an acetate-producing bacteria, can regulate intestinal local pH to maintain the stability of the chemical barrier (51). The butyrate-producing genus Roseburia is administered to improve the gut ecosystem and prevent leaky gut (65). ...
Sows exhibit metabolic syndrome and significant changes in intestinal microbiota during late gestation and lactation, affecting sow performance and piglet health. Dietary fiber (DF) is widely applied to improve sow performance by modulating gut microbiota and their by-products. Here, 60 sows were randomly allocated to groups, including CON (8% wheat bran), FBF-1 (1% fermented bamboo fiber), FBF-2 (2.5% fermented bamboo fiber), and FBF-3 (4% fermented bamboo fiber) from day 80 of gestation (G80d) to the end of lactation (L21d). Compared with CON, the FBF-3 diet decreased lactation backfat loss, increased average daily feed intake (ADFI) during lactation, and the weight gain of piglets, while supplementation of FBF increased fecal water content and reduced the rate of constipation in sows. Further, the yield and quality of milk of sows in FBF groups were improved. The FBF-3 diet significantly reduced markers of intestinal permeability (diamine oxidase and endotoxin) and systemic inflammation (interleukin-6 [IL-6] and tumor necrosis factor alpha) in sow serum during lactation, while it increased the anti-inflammatory marker (IL-10). Similarly, the piglets in the FBF-2 and FBF-3 groups had lower levels of IL-6 and higher levels of IgG, IgM, and insulin-like growth factor in serum. In addition, sows fed the 4% FBF diet had higher levels of acetate, propionate, butyrate, and total short-chain fatty acids (SCFAs) in feces than CON, and total SCFAs were promoted in piglets from the FBF-3 group. Spearman correlation analysis showed that immunity, inflammation, and intestinal microbiota are closely related to sow performance, which can affect piglet growth. The potential mechanism could be that FBF promoted the enrichment of beneficial genera such as Lachnospira, Lachnospiracea_XPB1014_Group, and Roseburia and the production of SCFAs in the sow's intestine, and reduced the relative abundance of harmful bacteria such as Fusobacterium, Sutterellaceae, and Sutterella. Meanwhile, the intake of FBF by sows affected the gut microbial composition of their offspring piglets, significantly increasing the relative abundance of beneficial bacteria Alistipes and Lachnoclostridium and decreasing the relative abundance of pathogenic bacteria Trueperella among colonic microorganisms. IMPORTANCE Dietary fiber is widely applied in the nutrition of sows due to its potential value in improving performance and intestinal health. Fermented bamboo fiber, rich in dietary fiber, has not been fully evaluated to be used in sow diets. Sows mobilize body reserves during gestation and lactation due to nutrients being prioritized for lactation purposes while feeding piglets, which generally leads to metabolism and immunity undergoing drastic changes. The main manifestations are increased inflammation and intestinal permeability and disturbed intestinal flora, which ultimately reduces the ADFI and milk quality, thus affecting the growth of piglets. The study described here is the first attempt to provide FBF for sows in late gestation and lactation can reverse this process. The 4% FBF was initially explored to have the most significantly beneficial effect. It provides a potentially effective method for dietary modification to control the gut microbiota and its metabolites to improve sow and piglet health. Moreover, the sow-piglet model offers a reference for investigating the impact of dietary fiber on the intestinal health of human mothers and infants.
... Clostridium cluster IX are propionate producers within the gut, and several species within this cluster can convert succinate to propionate (Gonzalez-Garcia et al. 2017). Additionally, several other species, including Megasphaera elsdenii and S. ruminantium can produce propionate from lactate (Hosseini et al. 2011, Gonzalez-Garcia et al. 2017. There was also a moderate increase in Bacteroides recorded in these vessels, and several strains within this genus encode the neces-sary methylmalonyl-CoA decarboxylase (mmdA) gene to utilize the succinate pathway (Reichardt et al. 2014). ...
... These results are similar to those documented previously (Carlson et al. 2017, Fehlbaum et al. 2018. This may potentially have significance to health given that propionate acts as a precursor in gluconeogenesis, improves satiety via stimulation of leptin production in adipocytes, and regulates cholesterol synthesis (Hosseini et al. 2011, Soty et al. 2015. ...
Aims:
In this study, we explored the effects that the prebiotic inulin-type fructans, and prebiotic candidates: 2'fucosyllactose and β-glucan from barley, singular and in combination had on microbial load, microbiome profile, and short-chain fatty acid production. This was carried out as a prescreening tool to determine combinations that could be taken forward for use in a human intervention trial.
Methods and results:
Effects of inulin-type fructans, 2'fucosyllactose and β-glucan from barley in singular and combination on microbial load and profile and short-chain fatty acid production (SCFA) was conducted using in vitro batch culture fermentation over 48 h. Changes in microbial load and profile were assessed by fluorescence in situ hybridization flow cytometry (FISH-FLOW) and 16S rRNA sequencing, and changes in SCFA via gas chromatography. All substrates generated changes in microbial load and profile, achieving peak microbial load at 8 h fermentation with the largest changes in profile across all substrates in Bifidobacterium (Q < 0.05). This coincided with significant increases in acetate observed throughout fermentation (Q < 0.05). In comparison to sole supplementation combinations of oligofructose, β-glucan and 2'fuscosyllactose induced significant increases in both propionate and butyrate producing bacteria (Roseburia and Faecalibacterium praunitzii), and concentrations of propionate and butyrate, the latter being maintained until the end of fermentation (all Q < 0.05).
Conclusions:
Combinations of oligofructose, with β-glucan and 2'fucosyllactose induced selective changes in microbial combination and SCFA namely Roseburia, F. praunitzii, propionate and butyrate compared to sole supplementation.
... All three SCFAs induce beneficial effects to the host epithelial cells and immune cells through the activation of intracellular and extracellular processes (Parada Venegas et al. 2019). Acetate, propionate and butyrate beneficially affect host energy and substrate metabolism through the secretion of gut hormones, including peptide YY and glucagon-like peptide-1, affecting appetite, slowing gastric emptying, enhancing insulin secretion and inhibiting glucagon secretion , Bridgeman et al. 2020, Hosseini et al. 2011. Furthermore, butyrate has epigenetic effects through inhibition of histone deacetylases and was found to confer numerous health benefits in animal models, including reduced serum triglycerides, total cholesterol and glucose, and reduced weight gain (Bridgeman et al. 2020). ...
... In addition, propionate was found to be an efficient substrate for glucose production in the liver (de Vadder and Mithieux 2018). Lastly, evidence suggests both butyrate and propionate exert an antiproliferative effect on colon cancer cells (Hosseini et al. 2011). ...
... Acetic acid, propionic acid and butyric acid are produced by intestinal microorganisms, and reduced levels of these short-chain fatty acids can trigger NAFLD by promoting gluconeogenesis and inflammation (11)(12)(13). Among these, propionate is the main product of dietary fiber fermentation in the colon, which is thought to reduce adipogenesis, serum cholesterol levels, and other tissue carcinogenic effects (14). It was found through repeated observations that when animals were fed fermentable fibers, they were prevented from steatosis induced by a high-fat diet, probably because propionate when absorbed from the portal vein, can alter hepatic metabolic processes to reduce lipid content (15). ...
... The up-regulated pathways in the rumen and colon were all related to glycolysis. L-rhamnose, a part of complex pectin polysaccharides, produced pyruvate upon degradation and increased propionate production in in vivo and in vitro studies (Hosseini et al., 2011). Mannan, a major component of plant hemicellulose (Moreira and Filho, 2008), promotes the glycolytic pathway, that is, the mixed acid (from glycolysis) fermentation to lactate, succinate, and acetate. ...
Grape pomace (GP), a by-product in wine production, is nutritious and can be used as a feed ingredient for ruminants; however, its role in shaping sheep gastrointestinal tract (GIT) microbiota is unclear. We conducted a controlled trial using a randomized block design with 10 Tan lambs fed a control diet (CD) and 10 Tan lambs fed a pelleted diet containing 8% GP (dry matter basis) for 46 days. Rumen, jejunum, cecum, and colon bacterial and archaeal composition were identified by 16S rRNA gene sequencing. Dry matter intake (DMI) was greater (p < 0.05) in the GP than CD group; however, there was no difference in average daily gain (ADG, p < 0.05) and feed conversion ratio (FCR, p < 0.05) between the two groups. The GP group had a greater abundance of Prevotella 1 and Prevotella 7 in the rumen; of Sharpe, Ruminococcaceae 2, and [Ruminococcus] gauvreauii group in the jejunum; of Ruminococcaceae UCG-014 and Romboutsia in the cecum, and Prevotella UCG-001 in the colon; but lesser Rikenellaceae RC9 gut group in the rumen and cecum, and Ruminococcaceae UCG-005 and Ruminococcaceae UCG-010 in the colon than the CD group. The pathways of carbohydrate metabolism, such as L-rhamnose degradation in the rumen, starch and glycogen degradation in the jejunum, galactose degradation in the cecum, and mixed acid fermentation and mannan degradation in the colon were up-graded; whereas, the pathways of tricarboxylic acid (TCA) cycle VIII, and pyruvate fermentation to acetone in the rumen and colon were down-graded with GP. The archaeal incomplete reductive TCA cycle was enriched in the rumen, jejunum, and colon; whereas, the methanogenesis from H2 and CO2, the cofactors of methanogenesis, including coenzyme M, coenzyme B, and factor 420 biosynthesis were decreased in the colon. The study concluded that a diet including GP at 8% DM did not affect ADG or FCR in Tan lambs. However, there were some potential benefits, such as enhancing propionate production by microbiota and pathways in the GIT, promoting B-vitamin production in the rumen, facilitating starch degradation and amino acid biosynthesis in the jejunum, and reducing methanogenesis in the colon.
... Acetic acid helps to regulate the acidbase balance of the gut and maintains the stability of the internal environment (Rosenstein et al., 1981). Propionate, another SCFA, provides health benefits such as lowering cholesterol, reducing fat storage, exhibiting anti-cancer properties and possessing antiinflammatory effects as a result of colonic bacteria fermentation (Hosseini et al., 2011). Butyrate is mainly produced by anaerobic bacteria like Eubacterium rectal and Faecalibacterium and serves as an important energy source in the colon (Chen et al., 2020). ...
Thousands of microorganisms reside in the human gut, and extensive research has demonstrated the crucial role of the gut microbiota in overall health and maintaining homeostasis. The disruption of microbial populations, known as dysbiosis, can impair the host’s metabolism and contribute to the development of various diseases, including cardiovascular disease (CVD). Furthermore, a growing body of evidence indicates that metabolites produced by the gut microbiota play a significant role in the pathogenesis of cardiovascular disease. These bioactive metabolites, such as short-chain fatty acids (SCFAs), trimethylamine (TMA), trimethylamine N-oxide (TMAO), bile acids (BAs), and lipopolysaccharides (LPS), are implicated in conditions such as hypertension and atherosclerosis. These metabolites impact cardiovascular function through various pathways, such as altering the composition of the gut microbiota and activating specific signaling pathways. Targeting the gut microbiota and their metabolic pathways represents a promising approach for the prevention and treatment of cardiovascular diseases. Intervention strategies, such as probiotic drug delivery and fecal transplantation, can selectively modify the composition of the gut microbiota and enhance its beneficial metabolic functions, ultimately leading to improved cardiovascular outcomes. These interventions hold the potential to reshape the gut microbial community and restore its balance, thereby promoting cardiovascular health. Harnessing the potential of these microbial metabolites through targeted interventions offers a novel avenue for tackling cardiovascular health issues. This manuscript provides an in-depth review of the recent advances in gut microbiota research and its impact on cardiovascular health and offers a promising avenue for tackling cardiovascular health issues through gut microbiome-targeted therapies.
... Propionic acid production in FL was slightly reduced, whereas butyric acid production was similar. Propionic acid receives attention for its regulating effects on lipogenesis, satiety, and the anti-proliferation of colon cancer cell lines [36]. Many of them overlap with acetic acid. ...
Gut microbiota has been described as a new ‘organ’ that interferes with host physiology by its metabolites produced from the utilization and biotransformation of undigested food components. Fu Ling (FL), the sclerotia of fungi Wolfiporia cocos, contains β-glucan, which is a known natural polysaccharide with strong medicinal efficacy. This study endeavors to evaluate the fermentability of FL and polysaccharides extracted from its sclerotia. An in vitro fermentation of structurally characterized FL and its β-glucan by human fecal microbiota was conducted. Total bacterial count, pH change, short-chain fatty acid profile and microbiota profile were assessed post-fermentation. FL containing over 70% of β-(1 → 3) and (1 → 6)-glucans with a low degree of branching of 0.24 could enhance acetic acid (a major microbial metabolite) production. Both FL and its extracted β-glucan had similar modulation on microbial composition. They enriched Phascolarctobacterium faecium, Bacteroides dorei and Parabacteroides distasonis, all of which are shown to possess anti-inflammatory effects. FL polysaccharide can be utilized as a natural whole food for its potential health benefits to human gut bacteria.
... The observed accumulation of butyrate in the GOS-containing treatments is probably due to the stimulation of butyrogenic microbiota within the microbiome by the GOS prebiotics [9]. In addition, the accumulating acetate might have favored the proliferation of members with the ability to metabolize it into butyrate and propionate [59,60], as observed in the GOS-treated groups between 12 and 24 h of incubation in our static in vitro fermentation model. ...
The objective of this study was to evaluate the effect of Lactobacillus amylovorus, L. plantarum, galacto-oligosaccharide (GOS) and their synbiotic formulations on pH, volatile fatty acids (VFA), malodor, and microbial ecological profiles through a 24-h in vitro fermentation model. Inclusion of GOS alone and in synbiotic combination with either probiotic resulted in consistently lower pH and higher total gas volumes at 12 and 24 h of incubation. Notably, concentrations of odorous compounds (hydrogen sulfide, H2S and methyl mercaptan, CH3SH) in the total gas produced were significantly lower in these GOS-containing treatments relative to the controls and probiotic-only-treated groups. However, although ammonia showed an initial relative reduction at 12 h, concentrations did not differ among treatments at 24 h. Further, the GOS-containing treatments had remarkably higher total and individual VFAs, including acetate, propionate, and butyrate, relative to controls and the probiotic-only treatments. Analysis of microbial composition and diversity showed clustering of GOS-containing treatments away from the controls and probiotic-only treatments at 12 and 24 h of incubation. Our study suggests that GOS supplementation (alone or in combination with L. amylovorus or L. plantarum probiotic strains) has the potential to increase VFA production in the swine gut while lowering emissions of malodorous compounds, except ammonia, in their manure.
... gluconeogenesis and in ammation [11][12][13]. Among these, propionate is the main product of dietary ber fermentation in the colon, which is thought to reduce adipogenesis, serum cholesterol levels, and other tissue carcinogenic effects [14]. It was found through repeated observations that when animals were fed fermentable bers, they were prevented from steatosis induced by a high-fat diet, probably because propionate, when absorbed from the portal vein, can alter hepatic metabolic processes to reduce lipid content [15]. ...
Background: The mechanisms of the effect of propionate metabolism and immunity on nonalcoholic fatty liver disease (NAFLD) have not been adequately studied.
Methods: Firstly, differentially expressed-propionate metabolism-related genes (DE-PMRGs) were selected by overlapping PMRGs and differentially expressed genes (DEGs) between the simple steatosis (SS) and health control (HC) groups. Then, common genes were selected by overlapping DE-PMRGs and key module genes obtained from weighted gene co-expression network analysis (WGCNA). Subsequently, the biomarkers were screened out by machine learning algorithms. The expression of the biomarkers was validated by quantitative Real-time PCR.
Results: In total, 5 biomarkers (JUN, LDLR, CXCR4, NNMT, and ANXA1) were acquired. The nomogram constructed based on 5 biomarkers had good predictive power for the risk of SS. Next, 5 biomarkers, 11 miRNAs, and 149 lncRNAs were encompassed in the ceRNA regulatory network. The expression of biomarkers was significantly higher in the HC group than in the SS group, which was consistent with the results in the GSE89632 and GSE126848 datasets.
Conclusions: In this study, 5 immune and propionate metabolism-related biomarkers (JUN, LDLR, CXCR4, NNMT, and ANXA1) were screened out to provide a basis for exploring the prediction of diagnosis of NAFLD.
... 30 Butyrate is recognized as one of the most important microbial metabolites produced in the gut because it is the main energy source for colonocytes and shows anti-inflammatory and anticarcinogenic effects. 31,32 In addition to butyrate, cashew fibers resulted in slightly higher propionate production, which has the ability to lower lipogenesis, serum cholesterol levels, and carcinogenesis, 33 over the course of the fermentation, compared to other nut fibers; however, a significant (p < 0.05) difference among nut groups was observed only between cashews and hazelnuts. Similarly, fermentation of cashews resulted in formation of a significantly higher amount of acetate, compared to almonds, hazelnuts, and pistachios, but not to walnuts. ...
This study aimed to evaluate and compare the effects of dietary fibers (DFs) of commercially important tree nuts (almond, cashew, hazelnut, pistachio, and walnut) on gut microbiota in vitro. Microbial compositions and short-chain fatty acids were determined using 16S rRNA sequencing and gas chromatography (GC), respectively. Neutral and acidic monosaccharides were analyzed using GC/MS and spectrophotometry, respectively. Our results revealed that cashew fibers exhibit higher butyrate formation compared to others. Accordingly, cashew fiber promoted butyric acid-producing bacteria-related operational taxonomic units (OTUs; Butyricimonas and Collinsella) at higher relative abundances. The higher butyrogenic capacity of cashew fiber is mainly attributed to its higher soluble/total DF ratio and remarkably distinct monosaccharide composition. Additionally, nut fibers stimulated family Lachnospiraceae- and Ruminococcaceae-related OTUs. These findings show that although the degree of promotion is nut type-dependent, nut fibers are generally capable of promoting beneficial microbes in the colon, further suggesting that DFs of tree nuts are contributing factors to their health-promoting effects.
... During the recovery period post-burn, metabolic pathways, particularly butanoate and propanoate metabolism, were significant enriched. SCFAs, particularly butyrate and propionate, are important links between the gut microbiome and the host and play a key role in maintaining intestinal health (Hosseini et al., 2011;Załęski et al., 2013;Louis and Flint, 2017;Zhang et al., 2021). Butyrate and propionate are mainly Analysis of microbial gene function prediction and dominant species contribution. ...
Introduction:
Burn injury has been shown to lead to changes in the composition of the gut microbiome and cause other damage in patients. However, little is known about how the gut microbial community evolves in individuals who have recovered from burn injury.
Methods:
In this study, we established a model of deep partial-thickness burn in mice and collected fecal samples at eight time points (pre-burn, 1, 3, 5, 7, 14, 21, and 28 days post-burn) for 16S rRNA amplification and high-throughput sequencing.
Results:
The results of the sequencing were analyzed using measures of alpha diversity, and beta diversity and taxonomy. We observed that the richness of the gut microbiome declined from day 7 post-burn and that the principal component and microbial community structure varied over time. On day 28 after the burn, the microbiome composition largely returned to the pre-burn level, although day 5 was a turning point for change. Some probiotics, such as the Lachnospiraceae_NK4A136_group, decreased in composition after the burn but were restored in the later recovery period. In contrast, Proteobacteria showed an opposite trend, which is known to include potential pathogenic bacteria.
Conclusion:
These findings demonstrate gut microbial dysbiosis after burn injury and provide new insights into the burn-related dysbiosis of the gut microbiome and strategies for improving the treatment of burn injury from the perspective of the microbiota.
... Acetate has been shown to alter intestinal cell apoptosis and mucus production (Liu et al., 2017). Propionate is also a potent fatty acid that modulate intestinal cell activity including differentiation and apoptosis (Hosseini et al., 2011). Lactate possesses diverse metabolic and regulatory properties, such as being an energy source and a signaling molecule for intestinal stem cell and goblet cell regeneration (Lee et al. 2018). ...
The present study aimed to investigate the effect of age, breed, and sex of broilers, as well as a probiotic or phytobiotic product on mucosal morphology, bacterial metabolites, and immune traits in the ileum of broilers. A total of 2,880 one-day-old male and female broiler chicks from two breeds (Ross308® and Cobb500®) were randomly assigned to 72 pens. Broilers were offered a wheat-soybean diet without (CO), or with either a probiotic (PO; 2.4 × 10⁹ CFU/kg of Bacillus subtilis DSM32324 and DSM32325 and B. amyloliquefaciens DSM25840) or a phytobiotic (PY; grape extract, 165 ppm procyanidin and 585 ppm polyphenols of the diet) product. The trial was conducted with a 3 × 2 × 2 factorial arrangement of diet, breed, and sex in a completely randomized design (6 replicate-pens per treatment). At day 7, 21, and 35, one chicken per pen was slaughtered for collecting ileal tissue to evaluate of histomorphology and mRNA expression, as well as ileal digesta to measure bacterial metabolites. Data were subjected to ANOVA (the main factors; age, diet, breed, and sex) and Four-Way ANOVA (interactions) using GLM procedure. Overall, the concentration of acetate and total short chain fatty acids reached the peak and lactate decreased to its lowest on day 21, but their concentrations at day 7 and 35 were similar (p > 0.05). Spermine, spermidine, and ammonia decreased after day 7, while putrescine and cadaverine increased after day 21 (p < 0.05). mRNA expression of cytokines, mucin 2 (MUC2) and claudin 5 (CLDN5) was similar; increased from day 7 to 21 and decreased afterward (p < 0.05). Villus height, crypt depth and villus surface area increased with age (p < 0.05). Acidic goblet cells (GC) number and density increased after day 21 (p < 0.05). Ross broilers showed higher D-lactate concentration and IFN-γ expression, while Cobb broilers had greater IL-4, IL-6 and TNF-α expression and higher total GC number (p < 0.05). Female displayed higher villus height and GC number and density (mixed and total GC) than male (p < 0.05). The effect of dietary treatment was not found on any investigated variables (p > 0.05). In conclusion, aging of broilers affected ileal histomorphology, cytokine expression, and barrier integrity, as well as bacterial activity. These observed impacts could be attributed to host-microbiota interaction and the direct effects of bacterial metabolites on intestinal cells and immune system.
... An In vitro study made in UHT milk demonstrated significant levels of propionate production (Table 5). Consequently, Renuspore R ingestion may increase propionate production in the gut and promote its anti-inflammatory properties and help lower lipogenesis and cholesterol levels in serum (Hosseini et al., 2011). Propionate production was likely linked to Renuspore R esterolytic activity, with genes encoding esterase A and lipases. ...
Exposure to diverse environmental pollutants and food contaminants is ever-increasing. The risks related to the bioaccumulation of such xenobiotics in the air and food chain have exerted negative effects on human health, such as inflammation, oxidative stress, DNA damage, gastrointestinal disorders, and chronic diseases. The use of probiotics is considered an economical and versatile tool for the detoxification of hazardous chemicals that are persistent in the environment and food chain, potentially for scavenging unwanted xenobiotics in the gut. In this study, Bacillus megaterium MIT411 (Renuspore®) was characterized for general probiotic properties including antimicrobial activity, dietary metabolism, and antioxidant activity, and for the capacity to detoxify several environmental contaminants that can be found in the food chain. In silico studies revealed genes associated with carbohydrate, protein and lipid metabolism, xenobiotic chelation or degradation, and antioxidant properties. Bacillus megaterium MIT411 (Renuspore®) demonstrated high levels of total antioxidant activities, in addition to antimicrobial activity against Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Campylobacter jejuni in vitro. The metabolic analysis demonstrated strong enzymatic activity with a high release of amino acids and beneficial short-chain fatty acids (SCFAs). Moreover, Renuspore® effectively chelated the heavy metals, mercury and lead, without negatively impacting the beneficial minerals, iron, magnesium, or calcium, and degraded the environmental contaminants, nitrite, ammonia, and 4-Chloro-2-nitrophenol. These findings suggest that Renuspore® may play a beneficial role in supporting gut health metabolism and eliminating unwanted dietary contaminants.
... Acetic acid is usually produced by a variety of microorganisms and reaches its highest concentration in the intestinal lumen [35]. Propionic acid is the primary metabolite of Bacteroides, which can affect the metabolism of the host liver and cholesterol [36], reduce serum and cholesterol levels [37], and prevent diet-induced obesity. Butyric acid is mainly produced by the metabolism of Bacteroidetes and Firmicutes, which is closely related to intestinal health [38]. ...
The probiotic role of lactic acid bacteria (LAB) in regulating intestinal microbiota to promote human health has been widely reported. However, the types and quantities of probiotics used in practice are still limited. Therefore, isolating and screening LAB with potential probiotic functions from various habitats has become a hot topic. In this study, 104 strains of LAB were isolated from and identified in traditionally fermented vegetables, fresh milk, healthy infant feces, and other environments. The antibacterial properties—resistance to acid, bile salts, and digestive enzymes—and adhesion ability of the strains were determined, and the biological safety of LAB with better performance was studied. Three LAB with good comprehensive performance were obtained. These bacteria had broad-spectrum antibacterial properties and good acid resistance and adhesion ability. They exhibited some tolerance to pig bile salt, pepsin, and trypsin and showed no hemolysis. They were sensitive to the selected antibiotics, which met the required characteristics and safety evaluation criteria for probiotics. An in vitro fermentation experiment and milk fermentation performance test of Lactobacillus rhamnosus (L. rhamnosus) M3 (1) were carried out to study its effect on the intestinal flora and fermentation performance in patients with inflammatory bowel disease (IBD). Studies have shown that this strain can effectively inhibit the growth of harmful microorganisms and produce a classic, pleasant flavor. It has probiotic potential and is expected to be used as a microecological agent to regulate intestinal flora and promote intestinal health. It can also be used as an auxiliary starter to enhance the probiotic value of fermented milk.
... Each elucidated ileal community comprises primary fermenters (e.g., Streptococcus, Enterococcus, and Lactobacillus) which metabolize simple carbohydrates into, e.g., lactate that supports growth of secondary fermenters (e.g., Veillonella). The latter consume lactate to produce shortchain fatty acids (SCFA; mainly acetate and propionate in the case of Veillonella) in a process termed cross-feeding (Foubert and Douglas, 1948;Egland et al., 2004;Hosseini et al., 2011;Scott et al., 2013;Kastl et al., 2020). ...
The human gastrointestinal tract consists of different regions, each characterized by a distinct physiology, anatomy, and microbial community. While the colonic microbiota has received a lot of attention in recent research projects, little is known about the small intestinal microbiota and its interactions with ingested compounds, primarily due to the inaccessibility of this region in vivo. This study therefore aimed to develop and validate a dynamic, long-term simulation of the ileal microbiota using the SHIME®-technology. Essential parameters were identified and optimized from a screening experiment testing different inoculation strategies, nutritional media, and environmental parameters over an 18-day period. Subjecting a synthetic bacterial consortium to the selected conditions resulted in a stable microbiota that was representative in terms of abundance [8.81 ± 0.12 log (cells/ml)], composition and function. Indeed, the observed community mainly consisted of the genera Streptococcus, Veillonella, Enterococcus, Lactobacillus, and Clostridium (qPCR and 16S rRNA gene targeted Illumina sequencing), while nutrient administration boosted lactate production followed by cross-feeding interactions towards acetate and propionate. Furthermore, similarly as in vivo, bile salts were only partially deconjugated and only marginally converted into secondary bile salts. After confirming reproducibility of the small intestinal microbiota model, it was integrated into the established M-SHIME® where it further increased the compositional relevance of the colonic community. This long-term in vitro model provides a representative simulation of the ileal bacterial community, facilitating research of the ileum microbiota dynamics and activity when, for example, supplemented with microbial or diet components. Furthermore, integration of this present in vitro simulation increases the biological relevance of the current M-SHIME® technology.
... More precisely, as acetate is incorporated into hepatocytes, acetyl-CoA synthase predominantly converts it to acetyl-CoA which afterward undergoes the cycle of cholesterol and fatty acid synthesis. Propionate by playing a competitive role toward the protein assigned for facilitating entrance of acetate into hepatocytes, decreases the synthesis of cholesterol and fatty acids (Hosseini et al. 2011). Hence, it seems that the ratio of acetate to propionate generated by GMB is a significant marker determining the lipid-lowering potential of prebiotics (Morrison et al. 2006). ...
Gut microbiota (GMB) in humans plays a crucial role in health and diseases. Diet can regulate the composition and function of GMB which are associated with different human diseases. Dietary fibers can induce different health benefits through stimulation of beneficial GMB. β-glucans (BGs) as dietary fibers have gained much interest due to their various functional properties. They can have therapeutic roles on gut health based on modulation of GMB, intestinal fermentation, production of different metabolites, and so on. There is an increasing interest in food industries in commercial application of BG as a bioactive substance into food formulations. The aim of this review is considering the metabolizing of BGs by GMB, effects of BGs on the variation of GMB population, influence of BGs on the gut infections, prebiotic effects of BGs in the gut, in vivo and in vitro fermentation of BGs and effects of processing on BG fermentability.
... Studies have shown that natural polymers such as polysaccharides and dietary fiber can generate SCFAs (the most abundant being acetate, propionate and butyrate) by microbial fermentation in the colon. It has been reported that acetate can enhance the protective function of host intestinal epithelial cells [84]; propionate has antilipogenic, anti-inflammatory, and anticarcinogenic activities [85]; butyrate is considered to be the main energy source of colonocytes, which can maintain intestinal integrity, regulate intestinal inflammation, and induce intestinal hormone secretion [68,69]. In this study, the intestinal epithelial and microbial dual targeting of the CUR@Chs-PNC NPs significantly promoted SCFA production compared with the DSS-induced colitis mice. ...
Curcumin (CUR) has a regulatory effect on the gut microbiota (GM), and its significant anti-inflammatory properties make it a research hotspot for inflammatory bowel disease (IBD) treatment. However, the low bioavailability and poor pharmacokinetic properties of CUR limit its practical application. Herein, CD44 and GM dual-targeted nanoparticles (NPs) loaded with CUR (CUR@Chs-PNC NPs) were derived from a quaternized chitosan and surface functionalization with chondroitin sulfate (Chs). The generated CUR@Chs-PNC NPs had an ideal average particle size (238.9 nm), a uniform size distribution, and a positive surface charge (+41.93 mV). Strikingly, the CUR@Chs-PNC NPs had a good sustained-release effect in a simulated gastrointestinal environment and exhibited the full drug release when in a simulated colon environment. Moreover, Chs functionalization endowed the NPs with a notable CD44-targeted drug delivery ability and thereby enhanced the CUR content in the plasma of SD rats. The biodistribution of the CUR@Chs-PNC NPs in vivo indicated that the NPs could prolong the intestinal residence time, thereby promoting the interaction between CUR and GM. Most importantly, in a DSS-induced colitis mouse model, the CUR@Chs-PNC NPs decreased the disease activity index, improved the oxidative stress and inflammation condition, promoted the production of short-chain fatty acids (SCFAs), regulated immune cells, and maintained intestinal microbiome homeostasis. This study demonstrates that CUR@Chs-PNC NPs, which exhibit excellent biocompatibility and biodegradability, on-demand drug release property, and CD44 and GM dual-targeted capacities, have the potential for further application in the treatment of colitis.
... Acetate is a key growth factor for some microbes as well as an important metabolite in host production of cholesterol and lipids. Propionate has a less well-defined role in the gut but plays an important role in the liver (Hosseini et al., 2011). Butyrate is an energy source for colonocytes (via b-oxidation to acetyl-CoA) and has been shown to play a role in helping to maintain the integrity of the gut epithelium via upregulation of Claudin-1 (a tight junction protein) in vitro (Clausen and Mortensen, 1995;Wang et al., 2012;Morrison and Preston, 2016). ...
The advent of immune checkpoint inhibitor therapy was a significant step in the development of treatments for cancer. It is, however, a double-edged sword. Immune related adverse events are the result of unleashing brakes on the immune system and affect many patients undergoing checkpoint inhibitor therapy, often being debilitating and occasionally lethal. It has been shown both in mice and in humans that the presence of certain families, genera and species of bacteria are associated with improved responses to checkpoint inhibitor therapy, whereas in their absence the response to therapy is often poor. Recent studies have demonstrated that immune related adverse events to checkpoint inhibitor therapy can be perturbed and perhaps predicted based on the composition and functional capacity of the gut microbiota and parts of the immune system. In the case of colitis associated with immune checkpoint inhibitor therapy, one interesting avenue of investigation is based on the activity of secretory immunoglobulin A (SIgA). Produced by plasma cells, IgA is present in high concentrations at the gut mucosa and is involved in both the maturation and maintenance of the microbiota as well as the development of IBD. Here we summarise the current literature surrounding the interplay between the gut microbiota and response to CPI therapy. Additionally, we overview the colonic immune system, paying particular attention to IgA, as a key component of the microbiota-immune system interaction.
... Propionate and butyrate are formed by specific bacterial groups that are of great interest due to their health benefits. The most important propionate-yielding microbiota in the human colon are still being discovered, and various metabolic routes for propionate production have been identified [141,142]. ...
... Two of these bacterial products, propionate, and acetate, have been proposed to influence several lipids metabolic pathways, including cholesterol synthesis, fatty acid synthesis, and fatty acid oxidation [38]. In addition, SCFAs may be involved in weight control by increasing the secretion of satiety-induced hormones such as glucagon-like peptide 1 and peptide YY (PYY) [39]. ...
To present a comprehensive synthesis of the effect of soluble fiber supplementation on blood lipid parameters in adults, a systematic search was undertaken in PubMed, Scopus, and ISI Web of Science of relevant articles published before November 2021. Randomized controlled trials (RCTs) evaluating the effects of soluble fibers on blood lipids in adults were included. We estimated the change in blood lipids for each 5 g/d increment in soluble fiber supplementation in each trial and then calculated the mean difference (MD) and 95% CI using a random-effects model. We estimated dose-dependent effects using a dose-response meta-analysis of differences in means. The risk of bias and certainty of the evidence was evaluated using the Cochrane risk of bias tool and the Grading Recommendations Assessment, Development, and Evaluation methodology, respectively. A total of 181 RCTs with 220 treatment arms (14,505 participants: 7348 cases and 7157 controls) were included. There was a significant reduction in LDL cholesterol (MD: -8.28 mg/dL, 95% CI: -11.38, -5.18), total cholesterol (TC) (MD: -10.82 mg/dL, 95% CI: -12.98, -8.67), TGs (MD: -5.55 mg/dL, 95% CI: -10.31, -0.79), and apolipoprotein B (Apo-B) (MD: -44.99 mg/L, 95% CI: -62.87, -27.12) after soluble fiber supplementation in the overall analysis. Each 5 g/d increase in soluble fiber supplementation had a significant reduction in TC (MD: -6.11 mg/dL, 95% CI: -7.61, -4.61) and LDL cholesterol (MD: -5.57 mg/dl, 95% CI: -7.44, -3.69). In a large meta-analysis of RCTs, results suggest that soluble fiber supplementation could contribute to the management of dyslipidemia and the reduction of cardiovascular disease risk.
... Propionic acid is hypothesized to lower lipogenesis in tissues (24). A study in mice found that administering propionic acid was protective against diet-induced obesity, insulin resistance, and reduced food intake (25). Furthermore, it is possible that having less propionic acid detected in the feces could indicate that more propionic acid is being absorbed in the gut and translocated to circulation. ...
Background
Plastic exposures have been shown to impact the microbiome, metabolism and growth of animals. However, no human studies have examined how plastic exposures are associated with fecal microbiota, microbial metabolites, or growth. Here we examine the association of plastic bottle feeding with infant fecal microbiota, microbial short-chain fatty acid (SCFA) metabolites, and anthropometry in the first year of life.
Methods
462 infants from the prospective Nurture Birth Cohort were included to examine frequency of plastic bottle feeding (every feeding vs. less than every feeding) at 3 months with anthropometric outcomes (skinfolds, length-for-age, and weight-for-length) at 1 year. A subset of 64 and 67 infants were included in analyses examining the fecal microbiota and fecal SCFAs, respectively. Microbial taxa were measured by 16S rRNA gene sequencing of the V4 region and SCFA concentrations were quantified using gas chromatography at 3 and 12 months of age.
Results
After adjustment for potential confounders, less frequent plastic bottle use was associated with lower fecal microbiota alpha Shannon diversity at 3 months (mean difference for plastic bottle used less than every feeding vs. every feeding = -0.53, 95% CI: -0.90, -0.17, p < 0.01) and lower propionic acid concentration at 3 months (mean log + 1 difference for plastic bottle used every feeding vs. less than every feeding = -0.53, 95% CI: -1.00, -0.06, p = 0.03). Furthermore, compared to infants who used plastic bottle at every feeding, infants who were plastic bottle-fed less frequently (1–3 times/day) at 3 months had significantly lower length-for-age z-scores at 12 months (mean difference= -0.40, 95% CI: -0.72, -0.07, p = 0.016).
Conclusion
Plastic bottle exposure may impact early infant gut microbiota and microbial SCFAs, which may in turn affect growth.
... Propionate is primarily used by the liver and converted into glucose. Hosseini et al. [49] suggested a prospective role of propionate in modulating the synthesis of cholesterol. Data in Table S3 showed significant differences (p ≤ 0.05) in the levels of detected major and minor short chain fatty acids. ...
Freeze-dried apple peel powder (Fd-APP) was subjected to in vitro digestion and colonic fermentation to evaluate the variations in its phenolic composition, bioactivities (antioxidant activity, α-amylase, and α-glucosidase inhibition) and fecal metabolic outputs. A total of 88 phenolics were tentatively identified, of which 51 phenolic compounds were quantitated in Fd-APP sample extracts before digestion, and 34 of them were released during subsequent phases of digestion. Among these, phenolic acids showed the highest bioaccessibility index (BI) of 68%, followed by flavonoids (63%) and anthocyanins (52%). The inhibitory functions of Fd-APP extracts against α-amylase and α-glucosidase pre and post digestion were moderate and ranged from 41.88 to 44.08 % and 35.23 to 41.13%, respectively. Additionally, the antioxidant activities revealed a significant (P≤0.05) decline during the in vitro digestion. However, the colonic fermentation stage presented different products where the intact parent phenolic compounds present in Fd-APP were utilized by gut microbes and produced various phenolic metabolites such 3- hydroxyphenyl acetic acid (3-HPAA), ferulic acid (F.A), 3-(4-hydroxyphenyl) propionic acid (3,4 HPPA) and 4- hydroxybenzoic acid (4-HBA). Furthermore, colonic fermentation of Fd-APP accelerated the production of short-chain fatty acids (SCFAs), with acetic acid being the most prevalent (97.53±9.09 mM). The decrease in pH of fermentation media to 4.3 significantly (p≤0.05) enhanced counts of Bifidobacterium (10.27 log CFU/ml), which demonstrated the potential prebiotic effects of Fd-APP. These findings indicated that consumption of apple peel as a constituent of novel functional foods, may support and protect the intestinal microbiota and consequently promote human health.
Gluco‐oligosaccharides (GlcOS) are potential prebiotics that positively modulate beneficial gut commensals like lactobacilli. For the rational design of GlcOS as prebiotics or combined with lactobacilli as synbiotics, it is important to establish the structure requirements of GlcOS and specificity toward lactobacilli. Herein, the utilization of 10 GlcOS with varied degrees of polymerization (DP) and glycosidic linkages by 7 lactobacilli strains ( Levilactobacillus brevis ATCC 8287, Limosilactobacillus reuteri ATCC PTA 6475, Lacticaseibacillus rhamnosus ATCC 53103, Lentilactobacillus buchneri ATCC 4005, Limosilactobacillus fermentum FUA 3589, Lactiplantibacillus plantarum WCFS1, and Lactobacillus gasseri ATCC 33323) was studied. L. brevis ATCC 8287 was the only strain that grew on α/β‐(1→4/6) linked disaccharides, whereas other strains showed diverse patterns, dependent on the availability of genes encoding sugar transporters and catabolic enzymes. The effect of DP on GlcOS utilization was strain dependent. β‐(1→4) Linked cello‐oligosaccharides (COS) supported the growth of L. brevis ATCC 8287 and L. plantarum WCFS1, and shorter COS (DP 2–3) were preferentially utilized over longer COS (DP 4–7) (consumption ≥90% vs. 40%–60%). α‐(1→4) Linked maltotriose and maltodextrin (DP 2–11) were effectively utilized by L. brevis ATCC 8287, L. reuteri ATCC 6475, and L. plantarum WCFS1, but not L. fermentum FUA 3589. Growth of L. brevis ATCC 8287 on branched isomalto‐oligosaccharides (DP 2–6) suggested preferential consumption of DP 2–3, but no preference between α‐(1→6) and α‐(1→4) linkages. The knowledge of the structure‐specific GlcOS utilization by different lactobacilli from this study helps the structural rationale of GlcOS for prebiotic development.
Bacterial metabolism in oral biofilms is comprised of complex networks of nutritional chains and biochemical regulations. These processes involve both intraspecies and interspecies networks as well as interactions with components from host saliva, gingival crevicular fluid, and dietary intake. In a previous paper, a large salivary glycoprotein, mucin MUC5B, was suggested to promote a dental health-related phenotype in the oral type strain of Streptococcus gordonii DL1, by regulating bacterial adhesion and protein expression. In this study, nuclear magnetic resonance-based metabolomics was used to examine the effects on the metabolic output of monospecies compared to dual species early biofilms of two clinical strains of oral commensal bacteria, S. gordonii and Actinomyces naeslundii , in the presence of MUC5B. The presence of S. gordonii increased colonization of A. naeslundii on salivary MUC5B, and both commensals were able to utilize MUC5B as a sole nutrient source during early biofilm formation. The metabolomes suggested that the bacteria were able to release mucin carbohydrates from oligosaccharide side chains as well as amino acids from the protein core. Synergistic effects were also seen in the dual species biofilm metabolome compared to the monospecies, indicating that A. naeslundii and S. gordonii cooperated in the degradation of salivary MUC5B. A better understanding of bacterial interactions and salivary-mediated regulation of early dental biofilm activity is meaningful for understanding oral biofilm physiology and may contribute to the development of future prevention strategies for biofilm-induced oral disease.
IMPORTANCE
The study of bacterial interactions and salivary-mediated regulation of early dental biofilm activity is of interest for understanding oral microbial adaptation to environmental cues and biofilm maturation. Findings in oral commensals can prove useful from the perspectives of both oral and systemic health of the host, as well as the understanding of general microbial biofilm physiology. The knowledge may provide a basis for the development of prognostic biomarkers, or development of new treatment strategies, related to oral health and disease and possibly also to other biofilm-induced conditions. The study is also an important step toward developing the methodology for similar studies in other species and/or growth conditions.
Propionate is a microbial metabolite formed in the gastrointestinal tract, and it affects host physiology as a source of energy and signaling molecule. Despite the importance of propionate, the biochemical pathways responsible for its formation are not clear in all microbes. For the succinate pathway used during fermentation, a key enzyme appears to be missing—one that oxidizes ferredoxin and reduces NAD. Here we show that Rnf [ferredoxin—NAD⁺ oxidoreductase (Na⁺-transporting)] is this key enzyme in two abundant bacteria of the rumen (Prevotella brevis and Prevotella ruminicola). We found these bacteria form propionate, succinate, and acetate with the classic succinate pathway. Without ferredoxin:NAD⁺ oxidoreductase, redox cofactors would be unbalanced; it would produce almost equal excess amounts of reduced ferredoxin and oxidized NAD. By combining growth experiments, genomics, proteomics, and enzyme assays, we point to the possibility that these bacteria solve this problem by oxidizing ferredoxin and reducing NAD with Rnf [ferredoxin—NAD⁺ oxidoreductase (Na⁺-transporting)]. Genomic and phenotypic data suggest many bacteria may use Rnf similarly. This work shows the ferredoxin:NAD⁺ oxidoreductase activity of Rnf is important to propionate formation in Prevotella species and other bacteria from the environment, and it provides fundamental knowledge for manipulating fermentative propionate production.
Rationale
Spleen‐qi deficiency syndrome, a common weakness syndrome in traditional Chinese medicine, results from insufficient spleen‐qi levels. For centuries, ginseng has been relied upon as a traditional Chinese medicine to treat spleen‐qi deficiency syndrome. Until now, the mechanism feature of ginseng in treating temper deficiency through intestinal bacteria and short‐chain fatty acid (SCFA) metabolites has not been fully elucidated.
Methods
This study established a rat model of spleen‐qi deficiency via multi‐factor compound modeling that involved fatigue injury and a controlled diet. The content of SCFAs between different treatment groups was determined by gas chromatography–mass spectrometry. And the 16s rRNA sequencing technology was applied to reveal the effects of ginseng on the intestinal microecological environment of the rats.
Results
It was found that the ginseng treatment group exhibited the most remarkable regulatory effect on propionic acid, surpassing all other administration groups. Ginseng increased the relative abundance of beneficial bacteria and decreased that of harmful bacteria at the genus level in rats with spleen‐qi deficiency syndrome. And propionic acid is significantly positively correlated with Lactobacillus level and significantly negatively correlated with uncultured_bacterium_f_Muribaculaceae ( p < 0.05). n ‐Butyric acid is negatively correlated with the Faecalibaculum level ( p < 0.01). n ‐Valeric acid is significantly negatively correlated with the Romboutsia level ( p < 0.01).
Conclusion
The mechanism of ginseng treatment for spleen‐qi deficiency is elucidated from the perspective of gut microbiota and its metabolite SCFAs. It provides a new way for further development and utilization of ginseng and a theoretical basis.
Insoluble dietary fiber (IDF) was recently revealed to have an antiobesity impact. However, the impact and potential mechanism of high-purity IDF derived from okara (HPSIDF) on obesity caused by a high-fat diet (HFD) remain unclear. Except for dietary supplementation, intermittent fasting (IF) has attracted extensive interest as a new dietary strategy against obesity. Thus, we hypothesize that HPSIDF combined with IF treatment may be more effective in preventing obesity. In this study, HPSIDF combined with IF treatment synergistically alleviated HFD-induced dyslipidemia, impaired glucose homeostasis, systemic inflammation, and fat accumulation. Furthermore, gut microbiota dysbiosis and lowered short-chain fatty acid synthesis were recovered by HPSIDF combined with IF treatment. Meanwhile, metabolomic analysis of feces revealed that HPSIDF combined with IF treatment obviously reversed the alterations of metabolic pathways and differential metabolites induced by HFD, which were linked to the modulations of the gut microbiota. Collectively, our findings indicated that HPSIDF combined with IF treatment has great potential to substantially enhance antiobesity efficacy by modulating the gut microbiota and its metabolites.
(1) Background: it is unclear whether serum vitamin B12 and circulating methylmalonic acid (MMA) are related with a poor prognosis among individuals with chronic kidney disease (CKD); (2) Methods: this prospective cohort study included 2589 individuals with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004, and from 2011 to 2014, respectively. Hazard ratios (HRs) and 95% Cis for the associations of MMA and vitamin B12 levels with the risk of all-cause and cardiovascular disease (CVD) mortality were calculated using multivariable Cox proportional hazards regression models. Restricted cubic spline analyses were used to examine the non-linear association of MMA levels with all-cause and CVD mortality. (3) Results: among the 2589 participants, we identified 1192 all-cause deaths and 446 CVD deaths, respectively, with a median follow-up of 7.7 years. Compared with participants with MMA < 123 nmol/L, those with MMA ≥ 240 nmol/L had an increased all-cause and CVD mortality in the multivariable-adjusted model [HR (95% CI), 2.01 (1.54-2.62) and 1.76 (1.18-2.63), respectively]; (4) Conclusions: higher circulating MMA levels were found to be strongly associated with an elevated all-cause and CVD mortality among individuals with CKD, while serum vitamin B12 levels were not associated.
Pomegranate, scientifically known as Punica granatum, has been a traditional medicinal remedy since ancient times. Research findings have shown that using pomegranate extracts can positively affect a variety of signaling pathways, including those involved in angiogenesis, inflammation, hyperproliferation, cellular transformation, the beginning stages of tumorigenesis, and lastly, a reduction in the final stages of metastasis and tumorigenesis. This is due to the fact that pomegranate extracts are rich in polyphenols, which are known to inhibit the activity of certain signaling pathways. In the United States, cancer is the second biggest cause of death after heart disease. The number of fatalities caused by cancer in the United States escalates yearly. Altering one's diet, getting involved in regular physical activity, and sustaining a healthy body weight are three easy steps an individual may follow to lower their cancer risk. Simply garnishing one's diet with vegetables and fruits has the potential to avert at least 20% of all cancer diagnoses and around 200,000 deaths caused by cancer each year. Vegetables, fruits, and other dietary constituents, such as minerals and phytochemicals, are currently being researched for their potential to prevent cancer. It is being done because they are safe, have minimal toxicity, possess antioxidant properties, and are universally accepted as dietary supplements. Ancient civilizations used the fruit of pomegranate (Punica granatum L.) to prevent and cure a number of diseases. The anti-tumorigenic, anti-inflammatory and anti-proliferative qualities of pomegranate have been shown in studies with the fruit, juice, extract, and oil of the pomegranate. Pomegranate has the capacity to affect several signaling pathways, which implies that it may have the potential to be employed not only as a chemopreventive agent but also as a chemotherapeutic drug. This article elaborates on some recent preclinical and clinical research which shows that pomegranate seems to have a role in the prevention and treatment of a number of cancers, including but not limited to breast, bladder, skin, prostate, colon, and lung cancer, among others.
The prevalence of obesity is growing worldwide and has been extensively linked to gut microbiota dysbiosis. In addition to exercise and physical activity, fiber-rich foods may be a first-line prophylactic to manage obesity. This study investigated in vivo dietary intervention with high-amylose maize starch (HAMS) and starch-entrapped microspheres (MS) to treat high-fat diet induced metabolic disorder and gut microbiome dysbiosis in mice. MS more efficiently controlled body weight as well as adipose tissue mass compared to HAMS. Furthermore, MS significantly reduced blood glucose, insulin, lipid and pro-inflammatory cytokine levels compared to the high-fat diet, while the effects of HAMS were less pronounced. The MS-altered gut microbiota composition favoring Streptococcaceae, Bacilli, Firmicutes and unclassified Clostridiales was predicted to promote fatty acid, pantothenate and Coenzyme A biosynthesis. In line with this, elevated fecal short chain fatty acid (SCFA), in particular, propionate concentration was observed in MS-fed mice. Our study provides novel insights into the mechanistic action of MS on intestinal homeostasis, providing a basis for future dietary therapeutic applications.
Thyroid disorders are clinically characterized by alterations of L-3,5,3',5'-tetraiodothyronine (T 4), L-3,5,3'-triiodothyronine (T 3), and/or thyroid-stimulating hormone (TSH) levels in the blood. The most frequent thyroid disorders are hypothyroidism, hyperthyroidism, and hypothyroxinemia. These conditions affect cell differentiation, function, and metabolism. It has been reported that 40% of the world's population suffers from some type of thyroid disorder and that several factors increase susceptibility to these diseases. Among them are iodine intake, environmental contamination, smoking, certain drugs, and genetic factors. Recently, the intestinal microbiota, composed of more than trillions of microbes, has emerged as a critical player in human health, and dysbiosis has been linked to thyroid diseases. The intestinal microbiota can affect host physiology by producing metabolites derived from dietary fiber, such as short-chain fatty acids (SCFAs). SCFAs have local actions in the intestine and can affect the central nervous system and immune system. Modulation of SCFAs-producing bacteria has also been connected to metabolic diseases, such as obesity and diabetes. In this review, we discuss how alterations in the production of SCFAs due to dysbiosis in patients could be related to thyroid disorders. The studies reviewed here may be of significant interest to endocrinology researchers and medical practitioners.
Single-nucleotide variation (SNV) imaging can indicate cellular heterogeneity and spatial pattern, but it remains challenging to produce high-gain signal while also yielding single-nucleotide resolution. Herein, we developed a light-up strategy for visualizing SNVs based on transcription amplification, enabling wash-free and high-contrast imaging of SNVs inside cells. The discrimination of SNVs is achieved by ligase-assisted transcription reaction. Employing a light-up RNA aptamer as a reporter eliminates nonspecific probe binding and the washing process and contributes to a 2-fold improvement of signal gain compared to that using the fluorescence in situ hybridization (FISH) method. The method allowed us to precisely quantify drug-resistant strains in the bacteria mixture and identify drug-resistant Salmonella enterica (S. enterica) isolated from poultry farm. Using this approach, we explored the colonization features of drug-resistant and drug-sensitive S. enterica in the mice intestinal tract and screened the prebiotics for Salmonella colonization inhibition. The SNV imaging method promises for the interrogation of genotypes in physiological and pathological states at the single-cell level.
The renin-angiotensin system (RAS) consists of multiple angiotensin peptides and performs various biological functions mediated by distinct receptors. Angiotensin II (Ang II) is the major effector of the RAS and affects the occurrence and development of inflammation, diabetes mellitus and its complications, hypertension, and end-organ damage via the Ang II type 1 receptor. Recently, considerable interest has been given to the association and interaction between the gut microbiota and host. Increasing evidence suggests that the gut microbiota may contribute to cardiovascular diseases, obesity, type 2 diabetes mellitus, chronic inflammatory diseases, and chronic kidney disease. Recent data have confirmed that Ang II can induce an imbalance in the intestinal flora and further aggravate disease progression. Furthermore, angiotensin converting enzyme 2 is another player in RAS, alleviates the deleterious effects of Ang II, modulates gut microbial dysbiosis, local and systemic immune responses associated with coronavirus disease 19. Due to the complicated etiology of pathologies, the precise mechanisms that link disease processes with specific characteristics of the gut microbiota remain obscure. This review aims to highlight the complex interactions between the gut microbiota and its metabolites in Ang II-related disease progression, and summarize the possible mechanisms. Deciphering these mechanisms will provide a theoretical basis for novel therapeutic strategies for disease prevention and treatment. Finally, we discuss therapies targeting the gut microbiota to treat Ang II-related disorders.
Nonpathogenic commensal microbiota and their metabolites and components are essential to maintain a tolerogenic environment and promote beneficial health effects. The metabolic environment critically impacts the outcome of immune responses and likely impacts autoimmune and allergic responses. Short-chain fatty acids (SCFAs) are the main metabolites produced by microbial fermentation in the gut. Given the high concentration of SCFAs in the gut and portal vein and their broad immune regulatory functions, SCFAs significantly influence immune tolerance and gut-liver immunity. Alterations of SCFA-producing bacteria and SCFAs have been identified in a multitude of inflammatory diseases. These data have particular significance in primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis because of the close proximity of the liver to the gut. In this focused review, we provide an update on the immunologic consequences of SCFA-producing microbiota and in particular on three dominant SCFAs in autoimmune liver diseases.
Background:
Functional constipation is an extremely common gastrointestinal disorder especially severely affecting the life quality of the aged. Jichuanjian (JCJ) has been widely used for aged functional constipation (AFC) in clinic. Yet, the mechanisms of JCJ merely scratch the surface with being studied at a single level, rather than from a systematic perspective of the whole.
Aim:
The purpose of this study was to explore the underlying mechanisms of JCJ in treating AFC from the perspectives of fecal metabolites and related pathways, gut microbiota, key gene targets and functional pathways, as well as "behaviors-microbiota-metabolites" relationships.
Methods:
16S rRNA analysis and fecal metabolomics combined with network pharmacology were applied to investigate the abnormal performances of AFC rats, as well as the regulatory effects of JCJ.
Results:
JCJ significantly regulated the abnormalities of rats' behaviors, the microbial richness, and the metabolite profiles that were interrupted by AFC. 19 metabolites were found to be significantly associated with AFC involving in 15 metabolic pathways. Delightfully, JCJ significantly regulated 9 metabolites and 6 metabolic pathways. AFC significantly interrupted the levels of 4 differential bacteria while JCJ significantly regulated the level of SMB53. HSP90AA1 and TP53 were the key genes, and pathways in cancer was the most relevant signaling pathways involving in the mechanisms of JCJ.
Conclusion:
The current findings not only reveal that the occurrence of AFC is closely related to gut microbiota mediating amino acid and energy metabolism, but also demonstrate the effects and the underlying mechanisms of JCJ on AFC.
Evidence has accumulated that gut microbiota and its metabolites, in particular the short-chain fatty acid propionate, are significant contributors to the pathogenesis of a variety of diseases. However, little is known regarding its impact on pediatric bronchial asthma, one of the most common allergic diseases in childhood. This study aimed to elucidate whether, and if so how, intestinal propionate during lactation is involved in the development of bronchial asthma. We found that propionate intake through breast milk during the lactation period resulted in a significant reduction of airway inflammation in the offspring in a murine house dust mite-induced asthma model. Moreover, GPR41 was the propionate receptor involved in suppressing this asthmatic phenotype, likely through the upregulation of Toll-like receptors. In translational studies in a human birth cohort, we found that fecal propionate was decreased one month after birth in the group that later developed bronchial asthma. These findings indicate an important role for propionate in regulating immune function to prevent the pathogenesis of bronchial asthma in childhood.
Omega-3 polyunsaturated fatty acids (PUFAs) and vitamins exert multiple beneficial effects on host health, some of which may be mediated through the gut microbiome. We investigated the prebiotic potential of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and lipid-soluble phylloquinone (vitamin K1), each at 0.2x, 1x and 5x using the simulator of the human intestinal microbial ecosystem (SHIME®) to exclude in vivo systemic effects and host-microbe interactions.Microbial community composition and, diversity [shotgun metagenomic sequencing] and microbial activity [pH, gas pressure, and production of short-chain fatty acids (SCFAs)] were measured over a period of 48 h. Fermentations supernatants were used to investigate the effect on gut barrier integrity using a Caco-2/goblet cell co-culture model.We found that EPA, DHA and vitamin K1 increased alpha-diversity at 24 h when compared with control. Moreover, there was an effect on beta-diversity with changes in gut microbial composition, such as an increase in the Firmicutes/Bacteroidetes (F/B) ratio and a consistent increase in Veillonella and Dialister abundances with all treatments. DHA, EPA, and vitamin K1 also modulated metabolic activity of the gut microbiome by increasing total SCFAs which was related mainly to an increase in propionate (highest with EPA and vitamin K1 at 0.2x). Finally, we found that EPA and DHA increased gut barrier integrity with DHA at 1x and EPA at 5x (p < 0.05, respectively). In conclusion, our in vitro data further establish a role of PUFAs and vitamin K to modulate the gut microbiome with effects on the production of SCFAs and barrier integrity.
The gut microbiota is believed to have a major impact on human health and disease. It is involved in barrier functions and maintenance of homeostasis. It provides nutrients and metabolites, participates in a signaling network, regulates epithelial development, and influences the immune system as well as protects the intestinal mucosa from the aggression of pathogenic microorganisms. There is growing evidence that physical activity has an impact on the gut microbiota. Recent studies in animals and humans suggest that regular physical activity increases the presence of beneficial microbial species and improves host health. However, some specific differences should be noted: different forms of physical activity, frequency or intensity, aerobic or resistance training, and benefits and consequences for amateur or competitive athletes. Because the positive role of physical activity can have an impact on health and various types of diseases, the results of research studies in this area are increasingly becoming the focus of scientific interest. In addition, probiotic supplements modulate intestinal microbial flora, and the ability of probiotics to modulate perturbations in immune function after exercise highlights their potential for use in individuals exposed to high levels of physical activity.
Sea cucumber sulfated polysaccharide (SCSPsj) is one of the dietary components which effectively modulates gut microbiota; however, the underlying mechanism remains unclear. In the present study, the interaction between SCSPsj and its utilizer (Parabacteroides distasonis) was investigated. Further study was carried out to explore the cross-feeding between intestinal Bacteroidales mediated by SCSPsj. The results revealed that SCSPsj can be fermented by P. distasonis to produce various microbial metabolites, including organic acids and derivatives, lipids and lipid-like molecules, organoheterocyclic compounds. SCSPsj can regulate the succinate pathway and acetyl-CoA pathway to influence the production of propanoic acid and acetic acid, respectively. Moreover, the SCSPsj-fermented supernatants of P. distasonis can only promote the growth of B. stercoris, B. vulgatus and P. johnsonii among 8 intestinal Bacteroidales strains through cross-feeding. The effect of cross-feeding was related to spatial distances and bacterial species. Moreover, the cross-feeding was correlated with compounds belonging to organic acids and derivatives, lipids and lipid-like molecules. These findings could provide new insights into the interaction between SCSPsj and gut microbiota.
The brain-gut axis forms a bidirectional communication system between the gastrointestinal (GI) tract and cognitive brain areas. Disturbances to this system in disease states such as inflammatory bowel disease have consequences for neuronal activity and subsequent cognitive function. The gut-microbiota-brain axis refers to the communication between gut-resident bacteria and the brain. This circuits exists to detect gut microorganisms and relay information to specific areas of the central nervous system (CNS) that in turn, regulate gut physiology. Changes in both the stability and diversity of the gut microbiota have been implicated in several neuronal disorders, including depression, autism spectrum disorder Parkinson's disease, Alzheimer's disease and multiple sclerosis. Correcting this imbalance with medicinal herbs, the metabolic products of dysregulated bacteria and probiotics have shown hope for the treatment of these neuronal disorders. In this review, we focus on recent advances in our understanding of the intricate connections between the gut-microbiota and the brain. We discuss the contribution of gut microbiota to neuronal disorders and the tangible links between diseases of the GI tract with cognitive function and behaviour. In this regard, we focus on irritable bowel syndrome (IBS) given its strong links to brain function and anxiety disorders. This adds to the growing body of evidence supporting targeted therapeutic strategies to modulate the gut microbiota for the treatment of brain/mental-health-related disease.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, debilitating disorder manifesting as severe fatigue and post-exertional malaise. The etiology of ME/CFS remains elusive. Here, we present a deep metagenomic analysis of stool combined with plasma metabolomics and clinical phenotyping of two ME/CFS cohorts with short-term (<4 years, n = 75) or long-term disease (>10 years, n = 79) compared with healthy controls (n = 79). First, we describe microbial and metabolomic dysbiosis in ME/CFS patients. Short-term patients showed significant microbial dysbiosis, while long-term patients had largely resolved microbial dysbiosis but had metabolic and clinical aberrations. Second, we identified phenotypic, microbial, and metabolic biomarkers specific to patient cohorts. These revealed potential functional mechanisms underlying disease onset and duration, including reduced microbial butyrate biosynthesis and a reduction in plasma butyrate, bile acids, and benzoate. In addition to the insights derived, our data represent an important resource to facilitate mechanistic hypotheses of host-microbiome interactions in ME/CFS.
Propionic acidemia (PA) is an inborn error of metabolism caused by the genetic deficiency of propionyl-CoA carboxylase (PCC).
By disrupting the α-subunit gene of PCC, we created a mouse model of PA (PCCA−/−), which died in 24–36 h after birth due to accelerated ketoacidosis. A postnatal, liver-specific PCC expression via a transgene
in a far lower level than that in wild-type liver, allowed PCCA−/− mice to survive the newborn and early infant periods, preventing a lethal fit of ketoacidosis (SAP+PCCA−/− mice). Interestingly, SAP+PCCA−/− mice, in which the transgene expression increased after the late infant period, continued to grow normally while mice harboring
a persistent low level of PCC died in the late infant period due to severe ketoacidosis, clearly suggesting the requirement
of increased PCC supplementation in proportion to the animal growth. Based on these results, we propose a two-step strategy
to achieve an efficient PA prevention in human patients: a partial PCC supplementation in the liver during the newborn and
early infant periods, followed by a larger amount of supplementation in the late infant period.
Arabinoxylooligosaccharides (AXOS) were enzymically produced on a large scale from commercial wheat bran. This implied enzyme-based removal of starch and proteins to yield an arabinoxylan (AX) enriched destarched, deproteinised wheat bran fraction, and further incubation of the latter with a Bacillus subtilis endoxylanase converting AX into AXOS. The recovered wheat bran AXOS had a purity of 72% and an average degree of polymerisation and degree of substitution of 15 and 0.27, respectively. Fractional precipitation with ethanol was effective in separating the wheat bran AXOS into fractions with different structure. At a given ethanol concentration, the degree of substitution, degree of polymerisation and substitution pattern of wheat bran AXOS all influenced their precipitation behaviour. Copyright © 2006 Society of Chemical Industry
Enteric methane (CH4) emission is a major contributor to Canadian greenhouse gas emissions, and also a loss of feed energy during production. The objective of this paper is to provide an update on current management practices and new dietary strategies recently proposed to reduce CH4 emissions from ruminants. Existing mitigation strategies for dairy, e.g., the addition of ionophores, fats, use of high-quality forages, and increased use of grains, have been well researched and applied. These nutritional changes reduce CH4 emissions by manipulating ruminal fermentation, directly inhibiting methanogens and protozoa, or by diverting hydrogen ions away from methanogens. Current literature has identified new CH4 mitigation options. These include the addition of probiotics, acetogens, bacteriocins, archaeal viruses, organic acids, plant extracts (e.g., essential oils) to the diet, as well as immunization, and genetic selection of cows. These new strategies are promising, but more research is needed to validate these approaches and to assess in vivo their effectiveness in reducing CH4 production by dairy cows. It is also important to evaluate CH4 mitigation strategies in terms of the total greenhouse gas budget and to consider the cost associated with the various strategies. More basic understanding of the natural differences in digestion efficiencies among animals as well as a better knowledge of methanogens and their interaction with other organisms in the rumen would enable us to exploit the potential of some of the new CH4 mitigation strategies for dairy cattle production.
Early epidemiological studies indicated that populations that consume a high proportion of non-starch polysaccharide (NSP) dietary fibre (DF) in their daily diet suffer less from gastrointestinal diseases, in particular colorectal cancers, than populations that consume diets that are high in fat and protein but low in NSP fibre. In this respect, diet, by increasing the amount of vegetables and NSP DF's, has been suggested to contribute as much as 25–35% to risk reduction for colorectal cancer. A reduction of fat intake may further reduce the risk by 15–25%. Based on these observations, DF's and substances that are part of the fibre complex such as antioxidants, flavonoids, sulphur containing compounds and folate have been proposed as potentially protective agents against colon cancer. However, results from controlled prospective studies in which beta-carotene and vitamin E or isolated dietary fibres were given to high risk groups showed disappointing results. There are recent indications that the regular consumption of certain subclasses of highly fermentable dietary fibre sources result in gut associated immune and flora modulation as well as a significant production of short chain fatty acids. In vitro studies as well as animal studies indicate that in particular propionate and butyrate have the potential to support the maintenance of a healthy gut and to reduce risk factors that are involved in the development of gut inflammation as well as colorectal cancer. A suggestion put forward is that beneficial effects may be obtained in particular by the consumption of resistant starch (RS) because of the high yield of butyrate and propionate when fermented. These SCFA are the prime substrates for the energy metabolism in the colonocyte and they act as growth factors to the healthy epithelium. In normal cells butyrate has been shown to induce proliferation at the crypt base, enhancing a healthy tissue turnover and maintenance. In inflamed mucosa butyrate stimulates the regeneration of the diseased lining of the gut. In neoplastic cells butyrate inhibits proliferation at the crypt surface, the site of potential tumour development. Moreover, models of experimental carcinogenesis in animals have shown the potential to modify a number of metabolic actions and steps in the cell cycle in a way that early events in the cascade of cancer development may be counteracted while stages of progression may be slowed down. The present review highlights a number of these aspects and describes the metabolic and functional properties of RS and butyrate.
PCR assays with primers targeted to the genes encoding 16S rRNA were developed for detection of dairy propionibacteria. Propionibacterium thoenii specific oligonucleotide PT3 was selected after partial resequencing. Tests allowed the detection of less than 10 cells per reaction from milk and cheese and 102 cells per reaction from forage and soil.
Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are anti-diabetes/obesity hormones secreted from the gut after meal ingestion. We have shown that dietary-resistant starch (RS) increased GLP-1 and PYY secretion, but the mechanism remains unknown. RS is a fermentable fiber that lowers the glycemic index of the diet and liberates short-chain fatty acids (SCFAs) through fermentation in the gut. This study investigates the two possible mechanisms by which RS stimulates GLP-1 and PYY secretion: the effect of a meal or glycemic index, and the effect of fermentation. Because GLP-1 and PYY secretions are stimulated by nutrient availability in the gut, the timing of blood sample collections could influence the outcome when two diets with different glycemic indexes are compared. Thus we examined GLP-1 and PYY plasma levels at various time points over a 24-h period in RS-fed rats. In addition, we tested proglucagon (a precursor to GLP-1) and PYY gene expression patterns in specific areas of the gut of RS-fed rats and in an enteroendocrine cell line following exposure to SCFAs in vitro. Our findings are as follows. 1) RS stimulates GLP-1 and PYY secretion in a substantial day-long manner, independent of meal effect or changes in dietary glycemia. 2) Fermentation and the liberation of SCFAs in the lower gut are associated with increased proglucagon and PYY gene expression. 3) Glucose tolerance, an indicator of increased active forms of GLP-1 and PYY, was improved in RS-fed diabetic mice. We conclude that fermentation of RS is most likely the primary mechanism for increased endogenous secretions of total GLP-1 and PYY in rodents. Thus any factor that affects fermentation should be considered when dietary fermentable fiber is used to stimulate GLP-1 and PYY secretion.
The effects of ispaghula and wheat bran on the contents of the caecum and proximal and distal colon of the rat were investigated to identify any differences that might account for their effects on colonic motility. Rats fed diets supplemented with 5% ispaghula and 10% wheat bran for 28 days were killed and the contents of the gut collected. Caecal and colonic content wet and dry weight and short chain fatty acid (SCFA) content were measured. In additional in vitro fermentations in batch cultures of mixed rat caecal bacteria with ispaghula and bran, SCFA production was monitored over 24 hours. Both ispaghula and wheat bran increased faecal weight but ispaghula was more effective. Ispaghula resulted in greater and more liquid contents, with a characteristic pattern of SCFA production (higher propionic acid) maintained throughout the colon. In contrast, wheat bran affected only the caecum and faeces. SCFA content and wet and dry weight in the proximal and distal colon were unaffected by wheat bran. Caecal butyrate was characteristically higher in wheat bran fed rats but ispaghula produced higher butyrate in the distal colon. In contrast, ispaghula seemed to be fermented more quickly in vitro than wheat bran. Thus, wheat bran has a portion that is rapidly fermented and an inert residue that may stimulate motility. Ispaghula seems to be fermented throughout the colon but maintains a high water content which dilutes the luminal contents.
Strain X4 was isolated several years ago from an anaerobic mesophilic plant treating vegetable cannery waste waters. It was the first example of propionic fermentation from ethanol. Morphologic and physiologic characterizations of the strain are presented here. This strain is described as type strain of a new species, Clostridium neopropionicum sp. nov. Whole cells of strain X4 ferment [1-13C] ethanol and CO2 to [2-13C] propionate, [1-13C] acetate and [2-13C] propanol, suggesting the absence of a randomizing pathway during the propionate formation. Enzymes involved in this fermentation were assayed in cell-free extracts of cells grown with ethanol as sole substrate. Alcohol dehydrogenase, aldehyde dehydrogenase, phosphate acetyl transferase, acetate kinase, pyruvate synthase, lactate dehydrogenases, and the enzymes of the acrylate pathway were detected at activities sufficient to be involved in ethanol fermentation. The same pathway may be used for the degradation of lactate or acrylate to acetate.
Incorporation of 3.3 g sodium propionate per 50 g available carbohydrate portion of bread reduced acutely the blood glucose response area in six healthy volunteers by 47.6 +/- 12.1% Similarly, in vitro digestibility was reduced by 47.4 +/- 1.1% (P less than 0.01). One week of dietary supplementation with 9.9 g sodium propionate in bread/d reduced the blood glucose area in comparison with standard propionate-free bread by 38.0 +/- 8.7% (P less than 0.05), but increased fecal bulk by 28.3 +/- 8.7% (P less than 0.05) and anaerobic microflora by 0.564 +/- 0.165 X 10(6)/g feces (P less than 0.05), specifically as bifidobacteria. Day-long breath hydrogen concentrations did not increase after 1 wk on propionate bread but methane production increased in the three methane producers. Although lipid changes were not significant, five subjects showed reduced high-density-lipoprotein and increased triglyceride concentrations, both of which correlated with increased fecal weight (P less than 0.05). Because propionate reduces the rate of starch digestion, studies using oral propionate must take into account its action as an enzyme inhibitor.
Evidence for the occurrence of microbial breakdown of carbohydrate in the human colon has been sought by measuring short chain fatty acid (SCFA) concentrations in the contents of all regions of the large intestine and in portal, hepatic and peripheral venous blood obtained at autopsy of sudden death victims within four hours of death. Total SCFA concentration (mmol/kg) was low in the terminal ileum at 13 +/- 6 but high in all regions of the colon ranging from 131 +/- 9 in the caecum to 80 +/- 11 in the descending colon. The presence of branched chain fatty acids was also noted. A significant trend from high to low concentrations was found on passing distally from caecum to descending colon. pH also changed with region from 5.6 +/- 0.2 in the caecum to 6.6 +/- 0.1 in the descending colon. pH and SCFA concentrations were inversely related. Total SCFA (mumol/l) in blood was, portal 375 +/- 70, hepatic 148 +/- 42 and peripheral 79 +/- 22. In all samples acetate was the principal anion but molar ratios of the three principal SCFA changed on going from colonic contents to portal blood to hepatic vein indicating greater uptake of butyrate by the colonic epithelium and propionate by the liver. These data indicate that substantial carbohydrate, and possibly protein, fermentation is occurring in the human large intestine, principally in the caecum and ascending colon and that the large bowel may have a greater role to play in digestion than has previously been ascribed to it.
Succinate is formed as an intermediate but not as a normal end product of the bovine rumen fermentation. However, numerous rumen bacteria are present, e.g., Bacteroides succinogenes, which produce succinate as a major product of carbohydrate fermentation. Selenomonas ruminantium, another rumen species, produces propionate via the succinate or randomizing pathway. These two organisms were co-cultured to determine if S. ruminantium could decarboxylate succinate produced by B. succinogenes. When energy sources used competitively by both species, i.e. glucose or cellobiose, were employed, no succinate was found in combined cultures, although a significant amount was expected from the numbers of Bacteroides present. The propionate production per S. ruminantium was significantly greater in combined than in single S. ruminantium cultures, which indicated that S. ruminantium was decarboxylating the succinate produced by B. succinogenes. S. ruminantium, which does not use cellulose, grew on cellulose when co-cultured with B. succinogenes. Succinate, but not propionate, was produced from cellulose by B. succinogenes alone. Propionate, but no succinate, accumulated when the combined cultures were grown on cellulose. These interspecies interactions are models for the rumen ecosystem interactions involved in the production of succinate by one species and its decarboxylation to propionate by a second species.
There are close parallels between the fermentative processes which go on in the rumen, caecum, and colon of herbivorous animals and colonic metabolism in man. Short chain fatty acids, which are the main end-product of carbohydrate breakdown in these organs, exert a controlling influence on intraluminal events, absorption, mucosal metabolism, and are accepted as such by animal physiologists. Such recognition has yet to be given to this aspect of colonic function in man, and many studies of colonic metabolism have failed to take account of the possible effect of short chain fatty acids. A great deal still needs to be learnt about these acids in the human colon - in particular, the overall amount produced each day, the main substrates for fermentation, the effect of diet, the molecular form in which they are absorbed, their contribution to energy metabolism, and their interaction with a wide range of other colonic events. Such knowledge should yield important information which may be relevant to the aetiology of colonic disorders which are so prevalent in the human species.
Restriction of dietary energy extends life and reduces incidences of disease in animals. These benefits would likely extend to humans. However, diet restriction in animals imposes reductions of 30-50% in food intake, which is probably unacceptable to humans. Low-energy sweeteners used in beverages offer minor reductions in energy intake. However, they lack the bulk required for baked goods and other sugar-rich foods. Full-bulk sweeteners providing about one-half the energy of sugar are under development for such uses. Laxation limits their acceptable dose. Even within such limitations, they can help achieve the health benefits for humans indicated by diet restriction. D-Tagatose, a new candidate sweetener, is nearly as sweet as sucrose and has the bulk of sucrose, yet provides zero available energy. We discuss its potential contribution to human diet restriction along with its specific effect in delaying the aging effects of glycosylation.
Propionate is a short-chain fatty acid formed in the colon and supposedly involved in the cholesterol-lowering effect of soluble fibre. To explore the underlying mechanism(s) of this fibre action, we have used human hepatocytes in primary culture to study the effects of propionate on hepatic lipid synthesis. Initial experiments with mevalonate and mevinolin, a competitive inhibitor of hydroxymethylglutaryl (HMG)-CoA reductase (EC 1.1.1.88) were performed to evaluate basic regulatory mechanisms in these cells; results were compared with those obtained with rat hepatocytes. Incubation for 24 h with mevalonate caused a similar, concentration-dependent inhibition of [14C]acetate incorporation into cholesterol in human and rat hepatocytes. Likewise, mevinolin (100 mumol/l) inhibited the formation of cholesterol from radiolabelled acetate by about 80% in cells from both species. Propionate inhibited cholesterol as well as triacylglycerol synthesis from [14C]acetate with a similar concentration-dependency in rat hepatocytes. Fifty percent inhibition was obtained at a propionate concentration of only 0.1 mmol/l. This propionate-induced inhibition was not affected by a 100-fold excess of unlabelled acetate. Human hepatocytes were much less susceptible in this respect: propionate concentrations of 10-20 mmol/l were required to obtain similar inhibitory effects in these cells, i.e. values greatly exceeding reported portal propionate concentrations in humans. The results suggest the existence of differences in the regulation of hepatic cholesterol (and triacylglycerol) synthesis between human and rat liver cells. These results do not support the hypothesis that the fibre-induced decrease in plasma cholesterol concentration in man is mediated by a direct effect of propionate on hepatic cholesterol synthesis.
The digestibility of D-tagatose, its effect on the digestibility of macronutrients and the metabolic response of the microbiota of the gastrointestinal tract to the ingestion of this carbohydrate were studied in pigs. Eight pigs were fed a low fiber diet comprising 15% sucrose (control group). Another eight pigs were fed a similar diet except that 100 g sucrose per kg diet was replaced by D-tagatose (test group). After 18 d, the pigs were killed and the gastrointestinal contents removed for analysis. The digestibility of D-tagatose was 25.8 +/- 5.6% in the distal third of the small intestine. The small intestinal digestibilities of dry matter (86.9 +/- 1.3 vs. 92.9 +/- 0.9%), gross energy (74.4 +/- 1.6 vs. 80.7 +/- 1.8%) and sucrose (90.4 +/- 2.5 vs. 98.0 +/- 0.5%) were lower (P < 0. 05) in the pigs fed D-tagatose. Digestibilities of starch, protein and fat did not differ between groups. D-Tagatose, sucrose and starch were fully digested in the large intestine. The fecal digestibilities of energy, dry matter and fat did not differ between the two groups, whereas D-tagatose reduced the fecal digestibility of protein (91.1 +/- 0.6 vs. 93.5 +/- 0.7%, P < 0.05). D-Tagatose served as a substrate for the microbiota in the cecum and proximal colon as indicated by a reduced pH, and a greater ATP concentration, adenylate energy charge (AEC) ratio and concentration of short-chain fatty acids. In particular, the increase in the concentrations of propionate, butyrate and valerate suggests possible health benefits of this monosaccharide.
The influence of sodium fumarate on rumen fermentation was investigated in vitro using batch and semi-continuous cultures of mixed rumen micro-organisms taken from three sheep receiving a basal diet of hay, barley, molasses, fish meal and a mineral-vitamin supplement (500, 299.5, 100, 91 and 9.5 g/kg DM respectively). Batch cultures consisted of 10 ml strained rumen fluid in 40 ml anaerobic buffer containing 200 mg of the same feed given to the sheep. Sodium fumarate was added to achieve a final concentration of 0, 5 or 10 mmol/l, as a result of the addition of 0, 250 or 500 mu mol, equivalent to 0, 200 and 400 g/kg feed. CH4 production at 24 h (360 mu mol in the control cultures) fell (P
This article unfortunately contained a mistake. The strain designations of two species, Prevotella brevis and Prevotella bryantii, were inadvertently reversed in Table 2. The names and sequences of the corresponding species-specific primers were not in error. The corrected table appears below.
Algal polysaccharides are indigestible and exhibit unusual biochemical and fermentative characteristics from which stem interesting biological effects such as antitumoral, immunostimulating and/or prebiotic effects. In this study, we aimed to determine whether oligosaccharides obtained from alginates and laminarans also have such biological activities and can thus be considered as functional foods. The chemical structures of the oligosaccharides were determined using NMR. Both the fermentation and the effects on microbial populations of oligo-alginates and oligo-laminarans were investigated using batch incubations with, and continuous culture of, human faecal bacteria. The kinetic and intensity of fermentation were measured by continuous monitoring of gas production and determination of final pH value, respectively. Effects on intestinal flora activity and composition were determined via metabolite quantification and main bacterial genera enumeration. Cytotoxic, proliferative and differentiating effects were estimated after exposure of epithelial (Caco-2), monocytic (THP1) and lymphocytic T (Jurkat) cell lines. Despite very different biochemical structures, the two oligo-alginates exhibited similar fermentation patterns. As with native alginates, they required adaptation prior to their metabolism. However, this adaptation did not result in any change in the global bacterial composition. No noticeable biological effect was detected for oligo-alginates, In contrast to native laminarans, oligo-laminarans did not require adaptation prior to their fermentation. Propionate production was stimulated but no significant modification of the balance between the main bacterial genera was observed during continuous culture of human fecal flora. Oligo-laminarans exhibited slightly inhibitory effects on Caco-2 cells, inhibited mononuclear cell proliferation and stimulated the expression of ICAM-1 by monocytic cells. This last property appears promising, and may allow algal oligosides to be used as functional foods and/or components.
Evidence for the occurrence of microbial breakdown of carbohydrate in the human colon has been sought by measuring short chain fatty acid (SCFA) concentrations in the contents of all regions of the large intestine and in portal, hepatic and peripheral venous blood obtained at autopsy of sudden death victims within four hours of death. Total SCFA concentration (mmol/kg) was low in the terminal ileum at 13 +/- 6 but high in all regions of the colon ranging from 131 +/- 9 in the caecum to 80 +/- 11 in the descending colon. The presence of branched chain fatty acids was also noted. A significant trend from high to low concentrations was found on passing distally from caecum to descending colon. pH also changed with region from 5.6 +/- 0.2 in the caecum to 6.6 +/- 0.1 in the descending colon. pH and SCFA concentrations were inversely related. Total SCFA (mumol/l) in blood was, portal 375 +/- 70, hepatic 148 +/- 42 and peripheral 79 +/- 22. In all samples acetate was the principal anion but molar ratios of the three principal SCFA changed on going from colonic contents to portal blood to hepatic vein indicating greater uptake of butyrate by the colonic epithelium and propionate by the liver. These data indicate that substantial carbohydrate, and possibly protein, fermentation is occurring in the human large intestine, principally in the caecum and ascending colon and that the large bowel may have a greater role to play in digestion than has previously been ascribed to it.
The effect of mannooligosaccharides (MOS) obtained from coffee mannan on cecal microbiota and short chain fatty acid production was examined in male Sprague-Dawley rats. The rats were given water and a dietary treatment containing 5% MOS ad libitum for 28 days. The body weight of those fed the MOS diet showed no significant difference compared with rats that consumed the control diet. The consumption of MOS increased the concentration of bifidobacteria (p < 0.05) and the ratio of bifidobacteria to total microbes (p < 0.05). The addition of MOS resulted in a significantly higher (p < 0.05) concentration of short chain fatty acids in the cecal contents compared with the control diet. The concentrations of acetate, propionate and butyrate were higher (p < 0.05) in rats fed the MOS diet compared with the control diet. These results suggest that MOS in the 5% diet promotes bifidobacteria growth and increased production of short chain fatty acids in rats.
Digestibility of mannooligosaccharides obtained from thermal hydrolysis of spent coffee grounds was examined by in vitro digestion method. Mannooligosaccharides were resistant to human salivary a-amylase, artificial gastric juice, porcine pancreatic enzymes and rat intestinal mucous enzymes. Fermentation products of mannooligosaccharides in human large intestine were estimated by in vitro fecal incubation method. Mannooligosaccharides were fermented by human fecal bacteria and the products of fermentation were short chain fatty acids. Acetic, propionic and n-butyric acids were the main short chain fatty acids as end fermentation products. These results suggest that mannooligosaccharides are indigestible saccharides and are converted to short chain fatty acids in human large intestine. The short chain fatty acids are thought to improve the large intestinal environment. Moreover, they are absorbed and utilized by the host as an energy source.
SUMMARY The mechanism of propionate formation by two strains of Selenomonas ruminantiurn has been investigated using substrates specifically labelled by 14C. Both strains behaved similarly. When (2-14C) lactate was fermented, the label in propionate was completely randomized in carbons 2 and 3. When cells were grown on lactate in the presence of 14C02, label was fixed exclusively into propionate carboxyl. The results are consistent with propionate being formed by the ' succinate' pathway.
Cellulose degradation and fermentation by the ruminal cellulolytic microorganism.Ruminococcus flavefaciensstrain 007,R. albusstrain 7 andNeocallimastix frontalisstrain MCH3 were studied in the absence and presence of acetogenic or sulfate-reducing ruminal bacteria. The presence of the H2-utilizing acetogens led to an increase in the cellulose breakdown by the two bacterial species and affected the kinetics of cellulose degradation byN. frontalis. The sulfate-reducing bacterium slightly increased cellulose degradation byR. albus, had no effect on cellulolysis byR. flavefaciensand inhibited the fungusN. frontalis. In the presence of the acetogens or sulfate-reducing bacteria there was a shift in the metabolism of the cellulolytic microorganisms towards greater production of acetate. Therefore, this study demonstrates that acetogens can interact with H2-producing cellulolytic microorganisms and that acetogenesis is a possible alternative to methanogenesis to eliminate H2from the ruminal ecosystem.
Both retinoic acid (RA) and sodium butyrate (NaB) induce differentiation in embryonal carcinoma F9 cells. Phenotypic changes caused by RA are irreversible, whereas those of NaB are rapid and reversible. In this study, we investigated the effects of combinations of these two agents on F9 cell differentiation and showed that RA had no effect on the cells induced to differentiate with NaB and vice versa. Thus, F9 cells are induced to differentiate along two distinct pathways which are mutually exclusive.
The short chain fatty acids acetate, propionate and butyrate are produced when dietary fibre is fermented by the colonic bacteria. We have previously shown that sodium butyrate induces apoptosis in 3 colorectal tumour cell lines. We have extended our study to 3 adenoma and 4 carcinoma cell lines and investigated whether propionate and acetate also induce apoptosis. All 3 short chain fatty acids induced apoptosis at physiological concentrations, but of the 3, butyrate was the most effective. Since these fatty acids are produced as a result of bacterial fermentation of dietary fibre, this may in part explain the correlation between a high-fibre diet and low colorectal cancer incidence. Sodium butyrate induced apoptosis in all 7 of the cell lines studied; however, 2 of the 4 carcinoma cell lines (PC/JW/F1 and S/KS/F1) were more resistant to butyrate-induced apoptosis than the 3 adenoma cell lines, suggesting that at least some carcinomas may evolve mechanisms to protect the cells from the induction of apoptosis. The bile acid deoxycholic acid has previously been reported as a possible tumour promoter in the large intestine and its levels are reduced by dietary fibre. Concentrations of between 10 nM and 0.1 mM had no effect on either the proliferation or apoptosis of colonic tumour cells in vitro. However, a significant induction of apoptosis was obtained at a concentration of 0.5 mM. These results may have significance for the aetiology of colorectal cancer. © 1995 Wiley-Liss, Inc.
Organic acids, and in particular short-chain fatty acids, are reported to have satiety-inducing effects. The aim of this study was to investigate if a dairy beverage containing propionic acid obtained by fermentation induces more satiety and a greater decrease in food intake than a non-fermented dairy product. In a within-subjects repeated-measures design, 43 young, healthy, normal-weight women consumed 150 mL, 1.0 MJ each of the fermented dairy beverage, a non-fermented dairy beverage (placebo) and a non-fermented dairy beverage with addition of 0.6% calcium propionate (positive control). Actual food intake of cold pasta salad was measured 25 min after finishing each preload. Subjects felt significantly fuller (F = 4.21; P = 0.02), were less hungry (F = 4.49; P = 0.004) and had less desire to eat (F = 5.34; P = 0.006) after consumption of the fermented dairy beverage and positive control compared with the placebo. However, there was no effect on ad libitum food consumption.
The effects of soluble corn bran arabinoxylans on cecal digestion, lipid metabolism, and mineral utilization [calcium (Ca) and magnesium (Mg)] were investigated in rats adapted to semipurified diets. The diets provided either 710 g/kg wheat starch alone (control) or 610 g/kg wheat starch plus 100 g/kg corn soluble fiber (arabinoxylans) and either 0 or 2 g/kg cholesterol (control + cholesterol and arabinoxylans + cholesterol, respectively). Compared with rats fed the control diets, rats fed the arabinoxylan diets had significant cecal hypertrophy (+50% after 3 days of the fiber adaptation) and an accumulation of short-chain fatty acids, especially propionic acid (up to 45% in molar percentage). Arabinoxylans enhanced the cecal absorption of Ca and Mg (from 0.07 to 0.19 micromol/min for Ca and from 0.05 to 0.23 micromol/min for Mg). Mg balance was enhanced by arabinoxylans (+25%). The arabinoxylan diet markedly reduced the cholesterol absorption from 50% of ingested cholesterol in controls up to approximately 15% in rats adapted to the arabinoxylans diet. Arabinoxylans were effective in lowering plasma cholesterol (approximately -20%). There was practically no effect of the diets on cholesterol in d > 1.040 lipoproteins (high density lipoproteins) whereas arabinoxylans were very effective in depressing cholesterol in d < 1.040 lipoproteins (especially in triglyceride-rich lipoproteins). Corn fermentable fiber decreased the accumulation of cholesterol in the liver. In parallel, the arabinoxylan diet counteracted the downregulation of 3-hydroxy-3-methylglutaryl-CoA by cholesterol. These data suggest that arabinoxylans may have a great impact on intestinal fermentation, mineral utilization, and cholesterol metabolism.
Perturbations in the gastrointestinal (GI) microbiota composition that occur as a result of antibiotics and diet in "westernized" countries are strongly associated with allergies and asthma ("hygiene hypothesis"). The microbiota ("microflora") plays a crucial role in the development of mucosal tolerance, including the airways. Significant attention has been focused on the role of the microbiota in GI development, immune adaptation and initiation of GI inflammatory diseases. This review covers the post-developmental functions that the microbiota plays in regulating immunological tolerance to allergen exposure outside the GI tract and proposes the question: is the microbiota a major regulator of the immune system?
The effects of inulin and alginate on intestinal microbial ecophysiology were investigated in piglets fed a diet (C) with 0.1% alginate (C+A) or 1.5% inulin (C+I) from weaning at day 28. The experiment was performed at an experimental farm (EF) and a commercial farm (CF). Digesta was collected from the ileum, caecum and colon of four piglets from each group on days 29, 30, 33 and 39. The metabolite concentrations changed with age. Colonic and caecal metabolites were affected by prebiotic treatment. Changes in microbiota composition were assessed by cultivation and denaturing gradient gel electrophoresis (DGGE) of 16S rRNA gene fragments. Enterococci increased in C+A at EF and decreased in C+I at both farms. Lactobacilli decreased in all segments in the experimental groups on days 30 and 33. Yeasts in C+I were five times lower at CF than at EF on day 39. The richness and diversity of DGGE profiles increased in the experimental groups. The evenness of colon digesta-derived DGGE profiles was higher in the experimental groups than in C and this situation was reversed in the distal small intestine. Multivariate redundancy analysis confirmed the recorded effects. In summary, both prebiotics affected the intestinal microbiota, and the changes were more pronounced at the CF.
Typewritten. Vita. Thesis (Ph. D.)--Cornell Univ., Sept. 1948. "References": leaves 37-40.
In this study, the prebiotic potential of arabinoxylan oligosaccharides (AXOS) was compared with inulin in two simulators of the human intestinal microbial ecosystem. Microbial breakdown of both oligosaccharides and short-chain fatty acid production was colon compartment specific, with ascending and transverse colon being the predominant site of inulin and AXOS degradation, respectively. Lactate levels (+5.5 mM) increased in the ascending colon during AXOS supplementation, while propionate levels (+5.1 mM) increased in the transverse colon. The concomitant decrease in lactate in the transverse colon suggests that propionate was partially formed over the acrylate pathway. Furthermore, AXOS supplementation strongly decreased butyrate in the ascending colon, this in parallel with a decrease in Roseburia spp. and Bacteroides/Prevotella/Porphyromonas (-1.4 and -2.0 log CFU) levels. Inulin treatment had moderate effects on lactate, propionate and butyrate levels. Denaturing gradient gel electrophoresis analysis revealed that inulin changed microbial metabolism by modulating the microbial community composition. In contrast, AXOS primarily affected microbial metabolism by 'switching on' AXOS-degrading enzymes (xylanase, arabinofuranosidase and xylosidase), without significantly affecting microbial community composition. Our results demonstrate that AXOS has a higher potency than inulin to shift part of the sugar fermentation toward the distal colon parts. Furthermore, due to its stronger propionate-stimulating effect, AXOS is a candidate prebiotic capable of lowering cholesterol and beneficially affecting fat metabolism of the host.
Cell suspensions of Bacteroides fragilis were allowed to ferment glucose and lactate labeled with (14)C in different positions. The fermentation products, propionate and acetate, were isolated, and the distribution of radioactivity was determined. An analysis of key enzymes of possible pathways was also made. The results of the labeling experiments showed that: (i) B. fragilis ferments glucose via the Embden-Meyerhof pathway; and (ii) there was a randomization of carbons 1, 2, and 6 of glucose during conversion to propionate, which is in accordance with propionate formation via fumarate and succinate. The enzymes 6-phosphofrucktokinase (pyrophosphate-dependent), fructose-1,6-diphosphate aldolase, phosphoenolpyruvate carboxykinase, malate dehydrogenase, fumarate reductase, and methylmalonyl-coenzyme A mutase could be demonstrated in cell extracts. Their presence supported the labeling results and suggested that propionate is formed from succinate via succinyl-, methylmalonyl-, and propionyl-coenzyme A. From the results it also is clear that CO(2) is necessary for growth because it is needed for the formation of C4 acids. There was also a randomization of carbons 1, 2, and 6 of glucose during conversion to acetate, which indicated that pyruvate kinase played a minor role in pyruvate formation from phosphoenolpyruvate. Phosphoenolpyruvate carboxykinase, oxaloacetate decarboxylase, and malic enzyme (nicotinamide adenine dinucleotide phosphate-dependent) were present in cell extracts of B. fragilis, and the results of the labeling experiments agreed with pyruvate synthesis via oxaloacetate and malate if these acids are in equilibrium with fumarate. The conversion of [2-(14)C]- and [3-(14)C]lactate to acetate was not associated with a randomization of radioactivity.
Plant fibers are the portions of plant foods that are not digested in the human small intestine. During this century, remarkable advances have been made in defining the characteristics and importance of most nutrients such as carbohydrate, proteins, fats, vitamins, and minerals. Plant fibers have largely been neglected because they considered to have no nutritive values. In the last decade, however, considerable attention has been focused on the various plant fibers because of their influence on gastrointestinal physiology. Evidence is emerging that plant fibers have profound influences on human nutrition because they alter the absorption and metabolism of many nutrients. We will review the evidence that plant fibers greatly influence the absorption and subsequent metabolism of carbohydrates and fats.