Modeling diet-gut microbiome interactions and prebiotic responses in Thai adults.

Short-chain fatty acid production and assimilation is unlikely to occur at significant levels in the newborn because the colon at birth is sterile, and only gradually acquires an anaerobic flora. This study profiled short-chain fatty acid levels in the colon lumen over the initial 21 days of life. Fecal samples were removed surgically from the cecum, right, and left colon from 36 York piglets, 0-21 days of life. Samples were subjected to in vitro dialysis and centrifugation methods to quantitate fecal water short-chain fatty acids, electrolytes, osmolality, and pH. A three-way analysis of variance examined piglet age, colon site of fecal samples, and method of fecal water analysis, for each variable. No differences were found between techniques of fecal water collection. Newborns showed production of short-chain fatty acids as early as the 1st day of life in limited amounts. Levels were stable between days 5 and 14, and then abruptly accumulated in the lumen. Acetate was predominant early, with propionate and butyrate responsible for late peaks. The production and assimilation of short-chain fatty acids was nearly complete proximal to the left colon. Age and colon site showed significant interactions for each fatty acid (p less than 0.001). The combined osmolar contributions of short-chain fatty acids and electrolytes accounted completely for the luminal osmolality after the 2nd wk of life. Previously there was an "osmolar gap" suggesting that lactose or its breakdown products were present in the lumen and were being removed by pathways other than through short-chain fatty acid production.

<h3></h3> The intestinal microbiota ferments complex carbohydrates that have not been broken down or absorbed during digestion into short-chain fatty acids (SCFA). SCFA are involved in different metabolic processes and the functioning of the immune system. Recent studies have shown changes in the SCFA profile in people with celiac disease (CD). Here we compared the composition of SCFA in the faecal water of the paediatric population with CD and the healthy children (HC). Faecal samples were obtained from 5 individuals with CD (2 female, 3 male) on a gluten-free diet (GFD) and 5 HC (3 female, 2 male) aged 13-18 years. To determine the SCFA concentrations sterile filtered fecal water was prepared. The SCFA profile was determined by gas chromatography. We compared the average SCFA concentrations between groups with CD and HC, for which we used the Student’s t-test. We also calculated the total SCFA and the fermentation index FI= (acetic acid – (propionic acid + butyric acid))/(the sum of SCFA). The comparison of concentrations of individual SCFA fractions showed a statistically significantly lower value of acetic acid (p = 0.04) and a statistically marginal increase in caproic acid concentration (p = 0.089) in the CD group. The averages of other SCFA were higher in healthy individuals but without statistical significance. Total SCFA was statistically significantly higher (p = 0.047) in HC. Fermentation index was 0.092 in HC and 0.079 in CD patients. The literature regarding the profile of SCFA in the paediatric population CD is scarce. Our results differ from the current literature, which reports a significant increase of acetic acid, total SCFA, and fermentation index in the paediatric population with CD compared to the control group. An increase in caproic acid in CD has not been reported yet. Recent studies have suggested that the study groups’ age difference or the amount of gluten in the diet could explain the discrepancies in our results.

Physico-chemical properties of purified starch affect their in vitro fermentation characteristics and are linked to in vivo fermentation characteristics in pigs

Dietary β-glucans from diverse sources exhibit varying prebiotic potentials, yet their comparative impacts on gut microbiota composition and short-chain fatty acid (SCFAs) production remain underexplored. This study investigated the effects of three β-glucans-oat, mushroom (Lentinula edodes), and curdlan-on gut microbiota modulation, and SCFA profiles in mice. Forty C57BL/6J mice were fed a low-fat diet supplemented with different β-glucans for 15 weeks. Gut microbiota composition was analyzed via 16S rRNA sequencing, and SCFAs levels were measured. Gut microbiota analysis revealed that oat β-glucan significantly reduced alpha diversity indices (observed species, ACE, and phylogenetic diversity) while increasing beneficial genera such as Prevotellaceae_UCG-001, Ruminiclostridium_5, Butyricicoccus, Ruminiclostridium_6, and Prevotellaceae_NK3B31_group. Oat β-glucan also elevated serum acetate, propionate, and lactate levels, whereas mushroom β-glucan selectively increased butyrate, and curdlan had no impact on SCFAs. Correlation analysis linked these SCFA enhancements to the enrichment of SCFA-producing bacteria (e.g., Ruminococcaceae, Lachnospiraceae). These findings highlight the source-dependent bioactivity of β-glucans, positioning oat β-glucan as a potent modulator of the gut-brain axis through microbiota-SCFA interactions, with implications for dietary interventions targeting metabolic and cognitive health.

Abstract. Waskita Y, Pangastuti A, Listyawati S, Sari SLA. 2024. Potency of tubers and rhizomes of java local foods as prebiotics and their effects toward bacterial diversity in mice cecum. Biodiversitas 25: 1544-1553. Tubers and rhizomes (TR) as Java local foods were less attention by people. Local foods contain IP (indigestible polysaccharides) content as prebiotic. The study aimed to analysis the prebiotic potency of TR extracts based on IP content and their effects toward increasing probiotic bacterial number, the TR extracts toward short-chain fatty acid (SCFA) profiles in probiotic media, and the TR extracts toward SCFA profiles and bacterial diversity in mice cecum. Tubers used were purple yam (Dioscorea alata var. purpurea), air potato (D. bulbifera), porang (Amorphophallus muelleri), Asiatic yam (D. esculenta), Asiatic bitter yam (D. hispida), white spot giant arum (A. paeoniifolius), yam bean (Pachyrizus erosus), and Hausa potato (Coleus rotundifolius). Rhizomes used were taro (Colocasia esculenta), arrowroot (Maranta arundinacea), and canna lilly (Canna indica). Work steps were extraction of TR, DNS assay, total sugar assay after acidic and enzymatic digestion, stimulation on increasing probiotic bacterial number (Lactobacillus plantarum and Bifidobacterium bifidum), SCFA production of probiotics, mice treatment, SCFA extraction in cecum, and determination of cecum bacterial communities. The highest IP contents were arrowroot, purple yam, air potato, porang, Asiatic yam, and taro extracts. These extracts except taro have higher IP content than inulin. The highest increasing probiotic bacterial number and SCFA production were shown by arrowroot extract rather than purple yam, air potato, and inulin. Bacteria communities had a high diversity value that showed micro-ecosystem balance in the cecum. Arrowroot was the same with inulin in increasing probiotics SCFA producers (Lachnospiraceae NK4A136, [Ruminococcus], Lactobacillus, Bacteroides, and Bifidobacterium) and decreasing pathogenic bacteria (Lachnoclostridium, Helicobacter, and Lawsonia) in mice cecum compared with control feed. Mucispirillum as a pathobiont-commensal had the same abundance in three feed treatments. Bacteria fermentation in the cecum produced the highest SCFA concentration in the 5% arrowroot feed treatment. Arrowroot had better prebiotic potency for the future.

Short chain fatty acids (SCFA) are the major products of carbohydrate fermentation by gut bacteria. Different carbohydrates are associated with characteristic SCFA profiles although the mechanisms are unclear. The individual SCFA profile may determine any resultant health benefits. Understanding determinants of individual SCFA production would enable substrate choice to be tailored for colonic SCFA manipulation. To test the hypothesis that the orientation and position of the glycosidic bond is a determinant of SCFA production profile, a miniaturized in vitro human colonic batch fermentation model was used to study a range of isomeric glucose disaccharides. Diglucose α(1-1) fermentation led to significantly higher butyrate production (p < 0.01) and a lower proportion of acetate (p < 0.01) compared with other α bonded diglucoses. Diglucose β(1-4) also led to significantly higher butyrate production (p < 0.05) and significantly increased the proportions of propionate and butyrate compared with diglucose α(1-4) (p < 0.05). There was no significant effect of glycosidic bond configuration on absolute propionate production. Despite some differences in the SCFA production of different glucose disaccharides, there was no clear relationship between SCFA production and bond configuration, suggesting that other factors may be responsible for promoting selective SCFA production by the gut microbiota from different carbohydrates.

Biotechnology is currently evolving through the era of big data, thanks to advances in the high-throughput technologies for rapid and inexpensive genome sequencing and other genome-wide studies [1]. With the daunting amount of data, it has been possible to put them together into a coherently organized biological network that provides counterintuitive insights on biological systems [2]. Among such biological networks, a genome-scale metabolic network model is expected to play an increasingly important role in the biopharmaceutical industry [3]. Before enumerating their specific strengths, it is important to note that principles underlying genome-scale metabolic network models are consistent with the holistic perspective of systems biology, the aim of which is to unveil hidden factors causing diseases and to find relevant treatment strategies [4]. Despite the importance of metabolism in a biological system, studies on diseases in relation to metabolism were far fewer in number than those performed on signaling and transcriptional regulatory networks [5]. However, metabolism, highly linked with observable phenotypes, is a biological network that is more comprehensively characterized when compared with the other two types of networks [6]. Metabolism is, therefore, amenable to large-scale mathematical modeling and simulation. It is with this motivation that the genome-scale metabolic simulation deserves more attention in drug discovery campaigns and optimization of a host strain for the production of biopharmaceuticals. Reconstruction and application of genome-scale metabolic network models have been forged as a major research strategy of systems biology. Over the last decade, genome-scale metabolic models have been built for almost all biologically important organisms across the domains of archea, bacteria and eukaryotes [3]. They range from simple micro organisms such as Escherichia coli [7] and Saccharomyces cerevisiae [8] to higher organisms including Chinese hamster ovary (CHO) cells [9,10] and a generic human cell [11,12]. It should be noted that all these organisms that have been subjected to metabolic modeling are important cellular hosts for biopharmaceutical production or medically meaningful organisms that need to be cured (e.g., specific cancer cells) or destroyed (e.g., pathogens). A recent notable development of importance in the genomescale metabolic modeling would be the newly updated human metabolic network Recon 2 [12]. Recon 2 is a result of efforts from a group of researchers, going over a vast amount of literature and biochemical data and reconciling conflicting information. Scope of the hitherto reconstructed genome-scale metabolic models manifest high expectations for their potential contributions to biopharmaceutical industry. Genome-scale metabolic network models are not just a simple pileup of biochemical reactions, but allow mathematical simulation under precisely defined conditions of constraints [13]. Once the experimentally Applications of genome-scale metabolic network models in the biopharmaceutical industry

Obesity contributes to hyperglycemia and metabolic dysfunction globally. Soybean and gembus tempeh, traditional Indonesian fermented foods, contain distinct dietary fiber compositions that may differentially influence metabolic outcomes through short-chain fatty acid (SCFA) production. However, comparative evidence regarding their metabolic effects is limited. This study aimed to compare the effects of soybean and gembus tempeh on obesity parameters, fasting blood glucose, and SCFA profiles in a rat model of hyperglycemic obesity. Methods: A randomized controlled pre–post trial was conducted at the Food and Nutrition Study Center, Universitas Gadjah Mada (April–June 2019). Forty-two rats were assigned to seven groups: normal, hyperglycemic-obese + AIN-93, AIN-93 + gembus tempeh, AIN-93 + soybean tempeh, high-fat high-fructose diet (HFFD), HFFD + gembus tempeh, and HFFD + soybean tempeh. The obesity index, fasting blood glucose, and SCFA concentrations were measured. Both types of tempeh significantly reduced the obesity index and fasting glucose levels in rats fed either the AIN-93 or HFFD diet, with greater reductions observed in the AIN-93 group (p &lt; 0.001). Butyrate levels were significantly higher in the tempeh-supplemented groups than in the control group (p &lt; 0.01), whereas propionate levels did not differ significantly (p = 0.079). In conclusion, soybean tempeh and gembus tempeh improved fasting glucose levels, obesity index, and SCFA production in hyperglycemic-obese rats. Gembus tempeh demonstrated a greater effect on reducing obesity index and fasting blood glucose than soybean tempeh.

There is an increasing interest in investigating dietary strategies able to modulate the gut microbial ecosystem which, in turn, may play a key role in human health. Dietary fibers (DFs) are widely recognized as molecules with prebiotic effects. The main objective of this systematic review was to: (i) analyze the results available on the impact of DF intervention on short chain fatty acids (SCFAs) production; (ii) evaluate the interplay between the type of DF intervention, the gut microbiota composition and its metabolic activities, and any other health associated outcome evaluated in the host. To this aim, initially, a comprehensive database of literature on human intervention studies assessing the effect of confirmed and candidate prebiotics on the microbial ecosystem was developed. Subsequently, studies performed on DFs and analyzing at least the impact on SCFA levels were extracted from the database. A total of 44 studies from 42 manuscripts were selected for the analysis. Among the different types of fiber, inulin was the DF investigated the most (n = 11). Regarding the results obtained on the ability of fiber to modulate total SCFAs, seven studies reported a significant increase, while no significant changes were reported in five studies, depending on the analytical methodology used. A total of 26 studies did not show significant differences in individual SCFAs, while the others reported significant differences for one or more SCFAs. The effect of DF interventions on the SCFA profile seemed to be strictly dependent on the dose and the type and structure of DFs. Overall, these results underline that, although affecting microbiota composition and derived metabolites, DFs do not produce univocal significant increase in SCFA levels in apparently healthy adults. In this regard, several factors (i.e., related to the study protocols and analytical methods) have been identified that could have affected the results obtained in the studies evaluated. Future studies are needed to better elucidate the relationship between DFs and gut microbiota in terms of SCFA production and impact on health-related markers.

Genome-scale community modeling for deciphering the inter-microbial metabolic interactions in fungus-farming termite gut microbiome

ObjectivesWe hypothesized that short chain fatty acid (SCFA) production by oral pathogens is suppressed by exposure to cigarette smoke extract (CSE).BackgroundTobacco smoking is a major risk factor for plaque‐induced periodontal diseases. Despite increased disease susceptibility, overt oral inflammation is suppressed in smokers, presenting a diagnostic conundrum. Bacterial‐derived SCFAs can penetrate into oral tissues where they influence multiple components of immune and healing responses. Indeed, the SCFA burden has been correlated with the inflammatory condition of the gingiva. However, the influence of cigarette consumption on SCFA production is unknown.MethodsGC/MS was employed to monitor the production of several SCFAs (propionic acid, isobutyric acid, butyric acid, and isovaleric acid) by representative anaerobic oral pathogens (Filifactor alocis 35896, Fusobacterium nucleatum 25586, Porphyromonas gingivalis 33277) that were exposed, or not, to a physiologically relevant dose of CSE (2000 ng/ml nicotine equivalents) generated from 3R4F reference cigarettes.ResultsThe growth of all three bacterial species was unaffected by CSE. The capacity to produce SCFAs by these bacteria was highly varied. F alocis produced the highest concentration of a specific SCFA (butyrate); P gingivalis provided the most robust overall SCFA signal, while F alocis and F nucleatum did not release detectable levels of isobutyrate or isovalerate. As P gingivalis 33277 was the broadest SCFA producer, three low‐passage clinical isolates (10208C, 5607, and 10512) were also examined. Compared to unconditioned microbes, reduced SCFA release was apparent in CSE‐exposed low‐passage clinical isolates of P gingivalis which reached significance for one of the three isolates (propionic, isobutyric, butyric, and isovaleric acids, all P < 0.05).ConclusionsThere is high disparity in the SCFA profiles of variant chronic periodontitis‐associated bacteria, while CSE exposure reduces SCFA production by a specific clinical strain of P gingivalis. If the latter phenomenon occurs in vivo, a reduced SCFA burden may help explain the reduced vascular response to dental plaque in tobacco smokers.

The ketogenic diet (KD) has been used for almost 100 years in the treatment of drug-resistant epilepsy in children - and adults. The intestinal microbiome has a climax character, and the main factor changing its composition and functions is the diet. Both increased biodiversity and the production of short-chain fatty acids (SCFAs) are important indicators of gut barrier function. SCFAs are synthesized by microorganisms through the fermentation of dietary fibre provided with the diet. They are an important element in signal transduction from the digestive system to other tissues. To date, there is little research to determine how the use of KD alters the SCFAs profile of the human stool. To assess the SCFAs profile in the stool of healthy and active KD users. Study group: amateur athletes following KD. Control group: amateur athletes following a regular diet (carbohydrates min. 50%); gender: men and women aged 18-60. Material: stool sample (1x10 g). SCFAs content was determined in stool samples using gas chromtography method. Participants completed a Food Frequency Questionnaire (FFQ) and a 72-hour food diary. There research has shown differences in the amount of SCFAs, as far as the results obtained from the two groups are concerned. The discrepancies referred to the levels of acetic, butyric, iso-butyric, valeric, and isovaleric acids. Spearman's rank correlation analysis showed a strong relationship between the consumption of selected dietary components (vegetables, fruits, red meat, poultry, fish, nuts and seeds, sugar, sugar substitutes, fats) and the SCFAs content in the stool of the study group. High consumption of cruciferous and leaf vegetables, berries and nuts on a ketogenic diet may have a positive effect on the profile of short-chain fatty acids produced by the gut microbiome. Changing the diet towards a greater supply of plant products may prevent proteolytic fermentation and reduce the negative effects of microbiome changes caused by an oversupply of protein and fat in the ketogenic diet.

Excretion of fecal short-chain fatty acids (SCFAs) may indicate changes in colonic or colonocyte metabolism. The aim of this study was to detect the influence of gestational age and feeding practices on SCFA concentrations and profiles in healthy preterm infants. A total of 198 fecal samples (28 infants) were collected from 8 to 21 days of age from 3 groups of preterm infants born at 33 to 37 weeks of gestation and fed either breast milk (group I) or Nutramigen, a lactose-free formula (group II), and extremely preterm infants born before 33 weeks of gestation and fed breast milk (group III). Total SCFA concentrations and SCFA profiles were analyzed using a gas chromographic (GC) procedure. Total fecal SCFA excretion did not differ significantly between group I (mean, 24.0 micromol/g; range, 1.3 to 118.8 micromol/g) and group II (mean, 23.0 micromol/g; range, 3.0 to 73.3 micromol/g). Conversely, differences occurred between SCFA profiles and became significant after day 17. The main differences were a significant increase in the butyric acid concentration (12% versus 30%) with group II. Compared with group I, fecal SCFA concentrations were 3.2-fold lower (7.4 micromol/g; range, 0.3 to 37.4 micromol/g) in group III with no significant changes in the profiles. Fecal SCFA excretion may vary in absence of any digestive disease. During this study, in terms of gestational age, total SCFA concentrations were significantly lower in extremely premature infants compared with infants born less premature, despite their known higher deficiency in intestinal lactase activity. In terms of diet, the absence of lactose did not lead to a decrease in colonic fermentation and induced changes in SCFA patterns. These new baseline data may offer clues to further development of milk formulas.

BackgroundMycophenolic acid (MPA) is the most widely used immunosuppressive drug in transplantation and for autoimmune diseases. Unfortunately, more than 30% of patients experience a typical gastrointestinal adverse effect also referred to as mycophenolate-induced enteropathy. Due to its antibacterial, antifungal, and antiviral properties, MPA exposure is associated with intestinal dysbiosis characterized by a decrease in density and diversity of the microbiome regarding the main bacterial phyla (Firmicutes and Bacteroidetes). These bacterial phyla are known for their metabolic role in maintaining the homeostasis of the digestive tract, particularly through the production of short-chain fatty acids (SCFA) that could contribute to the pathophysiology of mycophenolate-induced enteropathy. Our study aimed at deciphering short-chain fatty acids (SCFA) profile alterations associated with gastrointestinal toxicity of MPA at the digestive and systemic levels in a mouse model.MethodsTen-week old C57BL/6 (SOPF) mice were randomly assigned in 2 groups of 9 subjects: control, and mycophenolate mofetil (MMF, 900 mg/kg/day). All mice were daily treated by oral gavage for 7 days. Individual faecal pellets were collected at days 0, 4 and 8 as well as plasma at day 8 for SCFA profiling. Additionally, after the sacrifice on day 8, the caecum was weighted, and colon length was measured. The proximal colon was cut for histological analysis.ResultsMMF treatment induced around 10% weight loss at the end of the protocol associated with a significant decrease in caecum weight and a slight reduction in colon length. Histological analysis showed significant architectural changes in colon epithelium. Moreover, we observed an overall decrease in SCFA concentrations in faecal samples, especially regarding acetate (at day 8, control 1040.6 ± 278.161 μM versus MMF 384.7 ± 80.5 μM, p < 0.01) and propionate (at day 8, control 185.94 ± 51.96 μM versus MMF 44.07 ± 14.66 μM, p < 0.001), and in plasma samples for butyrate (at day 8, control 0.91 ± 0.1 μM versus MMF 0.46 ± 0.1 μM, p < 0.01).ConclusionsThese results are consistent with functional impairment of the gut microbiome linked with digestive or systemic defects during MMF treatment.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants associated with a wide variety of adverse human health outcomes. PCB 126 and PCB 153 are among the most prevalent congeners associated with human exposure. Emerging studies have suggested that PCB exposure leads to lower gut microbial diversity although their effects on microbial production of health promoting short-chain fatty acids (SCFAs) has been scarcely studied. Blue potatoes are rich in anthocyanins (ACNs), which is a class of polyphenols that promote the growth of beneficial intestinal bacteria such as Bifidobacterium and Lactobacillus and increase the generation of SCFAs. A batch-culture, pH-controlled, stirred system containing human fecal microbial communities was utilized to assess whether human gut microbiota composition and SCFA production are affected by: (a) PCB 126 and PCB 153 exposure; and (b) ACN-rich digests in the presence and absence of the PCB congeners. Anthocyanin-rich blue potato meals (11.03 g) were digested over 12 h with and without PCB 126 (0.5 mM) and PCB 153 (0.5 mM) using an in vitro simulated gut digestion model involving upper gastrointestinal digestion followed by metabolism by human fecal microbiota. Fecal digests were collected for analysis of gut microbial and SCFA profiles. Polychlorinated biphenyl-exposed fecal samples showed a significant (p < 0.05) decrease in species richness and a significantly (p < 0.05) different microbial community structure. PCB treatment was associated with an increased (p < 0.05) relative abundance of Akkermansia, Eggerthella, and Bifidobacterium and a decreased (p < 0.05) relative abundance of Veillonella, Streptococcus, and Holdemanella. ACN digests counteracted the altered abundances of Akkermansia and Bifidobacterium seen with the PCB treatment. PCB exposure was associated with a significant (p < 0.05) decrease in total SCFA and acetate concentrations. ACN digests were associated with significantly (p < 0.05) higher SCFA and acetate concentrations in the presence and absence of PCBs. Human fecal matter exposed to PCB 126 and PCB 153 led to decreased abundance and altered gut microbiota profiles as well as lowered SCFA and acetate levels. Importantly, this study showed that prebiotic ACN-rich potatoes counteract PCB-mediated disruptions in human gut microbiota profiles and SCFA production.