Bacterial Fermentation Products Research Articles

Targeted remodeling of the human gut microbiome using Juemingzi (Senna seed extracts).

The genus Senna contains globally distributed plant species of which the leaves, roots, and seeds have multiple traditional medicinal and nutritional uses. Notable chemical compounds derived from Senna spp. include sennosides and emodin which have been tested for antimicrobial effects in addition to their known laxative functions. However, studies of the effects of the combined chemical components on intact human gut microbiome communities are lacking. This study evaluated the effects of Juemingzi (Senna sp.) extract on the human gut microbiome using SIFR® (Systemic Intestinal Fermentation Research) technology. After a 48-hour human fecal incubation, we measured total bacterial cell density and fermentation products including pH, gas production and concentrations of short chain fatty acids (SCFAs). The initial and post-incubation microbial community structure and functional potential were characterized using shotgun metagenomic sequencing. Juemingzi (Senna seed) extracts displayed strong, taxon-specific anti-microbial effects as indicated by significant reductions in cell density (40%) and intra-sample community diversity. Members of the Bacteroidota were nearly eliminated over the 48-hour incubation. While generally part of a healthy gut microbiome, specific species of Bacteroides can be pathogenic. The active persistence of the members of the Enterobacteriaceae and selected Actinomycetota despite the reduction in overall cell numbers was demonstrated by increased fermentative outputs including high concentrations of gas and acetate with correspondingly reduced pH. These large-scale shifts in microbial community structure indicate the need for further evaluation of dosages and potential administration with prebiotic or synbiotic supplements. Overall, the very specific effects of these extracts may offer the potential for targeted antimicrobial uses or as a tool in the targeted remodeling of the gut microbiome.

Research status and prospect on the mechanisms of acupuncture and moxibustion treatment for constipation of Parkinson's disease.

Constipation may accelerate the progression of Parkinson's disease (PD). The quality of life in PD patients can be significantly improved when constipation is treated, hence the disease progression may be delayed. At present, the mechanism research is still at the initial stage for acupuncture in treatment of PD, focusing on neurohumoral factors, intestinal flora, bacterial fermentation products and intestinal inflammation； and there are the problems such as single intervention, thinking limitation and insufficient cooperation among disciplines. This paper systematically reviews the mechanism research progress of acupuncture for the treatment of constipation in PD so as to provide the references for the subsequent studies.

Butyrate enhances Clostridioides difficile sporulation in vitro.

Short-chain fatty acids (SCFAs) are products of bacterial fermentation that help maintain important gut functions such as maintenance of the intestinal barrier, cell signaling, and immune homeostasis. The main SCFAs acetate, propionate, and butyrate have demonstrated beneficial effects for the host, including its importance in alleviating infections caused by pathogens such as Clostridioides difficile. Despite the potential role of SCFAs in mitigating C. difficile infection, their direct effect on C. difficile remains unclear. Through a set of in vitro experiments, we investigated how SCFAs influence C. difficile growth, sporulation, and toxin production. Similar to previous studies, we observed that butyrate decreased growth of C. difficile strain 630 in a dose-dependent manner. The presence of butyrate also increased C. difficile sporulation, with minimal increases in toxin production. RNA-Seq analysis validated our experimental results, demonstrating increased expression of sporulation-related genes in conjunction with changes in metabolic and regulatory genes, such as a putative carbon starvation protein, CstA. Collectively, these data suggest that butyrate may induce alternative C. difficile survival pathways, modifying its growth ability and virulence to persist in the gut environment. IMPORTANCE Several studies suggest that butyrate may modulate gut infections, such as reducing inflammation caused by the healthcare-associated Clostridioides difficile. While studies in both animal models and human studies correlate high levels of butyrate with reduced C. difficile burden, the direct impact of butyrate on C. difficile remains unclear. Our study demonstrates that butyrate directly influences C. difficile by increasing its sporulation and modifying its metabolism, potentially using butyrate as a biomarker to shift survival strategies in a changing gut environment. These data point to additional therapeutic approaches to combat C. difficile in a butyrate-directed manner.

Moringa oleifera: A valuable insight into recent advances in medicinal uses and pharmacological activities.

Moringa oleifera is an important medicinal plant in several countries, e.g. Nigeria, USA, Turkey, Germany, Greece, and Ukraine. The abundant bioactive and nutritional properties of this plant make it useful in many and diverse areas of life including the health, cosmetic, agricultural and food industries to mention but a few. Research has found out that the presence of proteins, carbohydrates, lipids, vitamins, minerals, flavonoids, phenols, alkaloids, fatty acids, saponins, essential oils, folate, aromatic hydrocarbons, sterols, glucosinolates, glycosides among others characterise the Moringa- nutrient profile and as a result, give rise to its remedial effects on ailments such like wounds, stomach and duodenal ulcers, allergies, obesity, diabetics, inflammation, asthma, etcetera. It is the aim of this review to provide an insight into such medicinal and pharmacological remedies attributed to Moringa stating both the past and recent discoveries. This review article also takes a look into the botanical features, bioactive compounds, antinutrients, food applications, bacterial fermentation products, biosafety, industrial applications and other uses of Moringa. Finally, with belief that knowledge is progressive, we acknowledge that there are things yet undiscovered about this wonder plant that will be of value both to medicine and general life, we therefore recommend that research work continue on the plant Moringa. This article is protected by copyright. All rights reserved.

Mechanisms of carbonate precipitation induced by two model bacteria

The investigation of microbially induced calcium carbonate precipitation is essential to understanding CO2 fixation, marine carbonate rock formation, and biogeochemical cycling of life-essential elements. In this study, two model bacteria Bacillus subtilis (possess the cell wall of G+ bacteria) and Escherichia coli (possess the cell wall of G− bacteria) were used as representatives to induce carbonate mineralization. The mineralization ability of the two bacteria and carbonate precipitation mechanisms were studied with the biochemical analysis of bacterial fermentation products, mineral characterization, and biomimetic mineralization experiments. The results showed that both bacteria induced biomineral formation by using the cell wall as a template, but B. subtilis was more capable of inducing mineralization than E. coli. Particularly, the percentage of Ca2+ removal from the culture medium by the former reached 36% in 7 days, which induced the formation of vaterite and calcite, while that of Ca2+ removal by the latter reached 28%, and the resulting carbonate was amorphous calcium carbonate. Biomimetic mineralization experiments showed that protein molecules were the key factors inducing the formation of biological vaterite, while polysaccharides tended to bind small vaterite particles to form large organo-mineral aggregates. By comparing the results of inducing calcium carbonate under the same culture conditions, the two types of bacteria with completely different cell wall structures had significant differences in the ability to induce calcium carbonate synthesis, among which that was stronger by Bacillus subtilis (G+) than by Escherichia coli (G−). It was found that factors such as bacterial cell wall structure, extracellular secretions including carbonic anhydrase, pH value, etc. all affect the microbial-induced carbonate precipitation to varying degrees, providing new insights into the theory of bacterial-induced carbonate mineralization.

Mitochondrial nanomotion measured by optical microscopy.

Nanometric scale size oscillations seem to be a fundamental feature of all living organisms on Earth. Their detection usually requires complex and very sensitive devices. However, some recent studies demonstrated that very simple optical microscopes and dedicated image processing software can also fulfill this task. This novel technique, termed as optical nanomotion detection (ONMD), was recently successfully used on yeast cells to conduct rapid antifungal sensitivity tests. In this study, we demonstrate that the ONMD method can monitor motile sub-cellular organelles, such as mitochondria. Here, mitochondrial isolates (from HEK 293 T and Jurkat cells) undergo predictable motility when viewed by ONMD and triggered by mitochondrial toxins, citric acid intermediates, and dietary and bacterial fermentation products (short-chain fatty acids) at various doses and durations. The technique has superior advantages compared to classical methods since it is rapid, possesses a single organelle sensitivity, and is label- and attachment-free.

The deterrent ability of Xenorhabdus nematophila and Photorhabdus laumondii compounds as a potential novel tool for Lobesia botrana (Lepidoptera: Tortricidae) management

The grapevine moth, Lobesia botrana (Lepidoptera: Tortricidae), is a critical pest for vineyards and causes significant economic losses in wine-growing areas worldwide. Identifying and developing novel semiochemical cues (e.g. volatile bacterial compounds) which modify the ovipositional and trophic behaviour of L. botrana in vineyard fields could be a novel control alternative in viticulture. Xenorhabdus spp. and Photorhabdus spp. are becoming one of the best-studied bacterial species due to their potential interest in producing toxins and deterrent factors. In this study, we investigated the effect of the deterrent compounds produced by Xenorhabdus nematophila and Photorhabdus laumondii on the ovipositional moth behaviour and the larval feeding preference of L. botrana. Along with the in-vitro bioassays performed, we screened the potential use of 3 d cell-free bacterial supernatants and 3 and 5 d unfiltered bacterial ferments. In addition, we tested two application systems: (i) contact application of the bacterial compounds and (ii) volatile bacterial compounds application. Our findings indicate that the deterrent effectiveness varied with bacterial species, the use of bacterial cell-free supernatants or unfiltered fermentation product, and the culture times. Grapes soaked in the 3 d X. nematophila and P. laumondii ferments had ∼ 55% and ∼ 95% fewer eggs laid than the control, respectively. Likewise, the volatile compounds emitted by the 5 d P. laumondii fermentations resulted in ∼ 100% avoidance of L. botrana ovipositional activity for three days. Furthermore, both bacterial fermentation products have larval feeding deterrent effects (∼65% of the larva chose the control grapes), and they significantly reduced the severity of damage caused by third instar larva in treated grapes. This study provides insightful information about a novel bacteria-based tool which can be used as an eco-friendly and economical alternative in both organic and integrated control of L. botrana in vineyard.

Low expression of the intestinal metabolite butyric acid and the corresponding memory pattern regulate HDAC4 to promote apoptosis in rat hippocampal neurons

After intensive research on the gut-brain axis, intestinal dysbiosis is considered to be one of the important pathways of cognitive decline. Microbiota transplantation has long been thought to reverse the behavioral changes in the brain caused by colony dysregulation, but in our study, microbiota transplantation seemed to improve only behavioral brain function, and there was no reasonable explanation for the high level of hippocampal neuron apoptosis that remained. Butyric acid is one of the short-chain fatty acids of intestinal metabolites and is mainly used as an edible flavoring. It is commonly used in butter, cheese and fruit flavorings, and is a natural product of bacterial fermentation of dietary fiber and resistant starch in the colon, acting similarly to the small-molecule HDAC inhibitor TSA. The effect of butyric acid on HDAC levels in hippocampal neurons in the brain remains unclear. Therefore, this study used rats with low bacterial abundance, conditional knockout mice, microbiota transplantation, 16S rDNA amplicon sequencing, and behavioral assays to demonstrate the regulatory mechanism of short-chain fatty acids on the acetylation of hippocampal histones. The results showed that disturbance of short-chain fatty acid metabolism led to high HDAC4 expression in the hippocampus and regulated H4K8ac, H4K12ac, and H4K16ac to promote increased neuronal apoptosis. However, microbiota transplantation did not change the pattern of low butyric acid expression, resulting in maintained high HDAC4 expression in hippocampal neurons with continued neuronal apoptosis. Overall, our study shows that low levels of butyric acid in vivo can promote HDAC4 expression through the gut-brain axis pathway, leading to hippocampal neuronal apoptosis, and demonstrates that butyric acid has great potential value for neuroprotection in the brain. In this regard, we suggest that patients with chronic dysbiosis should pay attention to changes in the levels of SCFAs in their bodies, and if deficiencies occur, they should be promptly supplemented through diet and other means to avoid affecting brain health.

Cryptosporidium infection induced the dropping of SCFAS and dysbiosis in intestinal microbiome of Tibetan pigs.

The infection of Cryptosporidium in pigs causes digestive system ailments, diarrhea and weight loss serving as an economic burden, especially in newborn animals. The bacterial fermentation products of short-chain fatty acids have important roles in immune function, microbiota regulation, osmotic balance and metabolism. However, till now little knowledge is available about the effect of Cryptosporidium infection on microbiota and SCFAs in plateau pigs. Hence, we performed this study to explore the response of microbiota and SCFAs in the natural infection of Cryptosporidium in Tibetan pigs. Cryptosporidium positive (infected, G) and negative samples (healthy, J) in our previous study were used for high throughputsequencing and Gas Chromatography-Mass Spectrometer analysis. Over 81000 and 74000 filtered sequences were detected in healthy and infected Tibetan pigs, respectively. Lower sample richness and evenness were observed in Cryptosporidium infection, as alpha diversity analysis found that chao1 (p<0.05), faith_pd (p<0.05), and observed_features in group G were significantly lower than pigs in group J. A total of 4 and 27 significant different phyla and genera were found between group G and J. The changed genera were Psychrobacter, Desemzia, Succiniclasticum, Treponema, Campylobacter, Atopobium, Olsenella, Pediococcus, Peptococcus, Sharpea, Desulfovibrio, Acinetobacter, Rhodococcus, Anaerostipes, Turicibacter, Lactobacillus, RFN20, Phascolarctobacterium, Roseburia, Megasphaera, Streptococcus, Blautia, Lachnospira, rc4_4, Gemmiger, Dorea, Oribacterium and Prevotella, which affected the microbiota functions with 360 abundance changed enzymes, and pathways in L1, L2 and L3 levels of KEGG. The concentration of acetic acid (p<0.01), butyric acid (p<0.05) and caproic acid (p<0.01) were lower in group G. In conclusion, the present study herein uncovered that the host responses to Cryptosporidium infection in Tibetan pigs with 27 of significantly changed genera decreased SCFAs in pigs, which may provide insights in further developing novel therapy against this protozoan.

Protective role of butyrate in obesity and diabetes: New insights.

Studies in human microbiota dysbiosis have shown that short-chain fatty acids (SCFAs) like propionate, acetate, and particularly butyrate, positively affect energy homeostasis, behavior, and inflammation. This positive effect can be demonstrated in the reduction of butyrate-producing bacteria observed in the gut microbiota of individuals with type 2 diabetes (T2DM) and other energy-associated metabolic alterations. Butyrate is the major end product of dietary fiber bacterial fermentation in the large intestine and serves as the primary energy source for colonocytes. In addition, it plays a key role in reducing glycemia and improving body weight control and insulin sensitivity. The major mechanisms involved in butyrate regulation include key signaling pathways such as AMPK, p38, HDAC inhibition, and cAMP production/signaling. Treatment strategies using butyrate aim to increase its intestine levels, bioavailability, and improvement in delivery either through direct supplementation or by increasing dietary fiber in the diet, which ultimately generates a higher production of butyrate in the gut. In the final part of this review, we present a summary of the most relevant studies currently being carried out in humans.

Bacterial and fungal microbiota of total mixed ration silage stored at various temperatures.

To obtain insights into how bacterial and fungal microbiota and fermentation products composition are affected by storage temperature for TMR silage, which can be manufactured year-round. TMR silage was stored at 10°C, 25°C, ambient temperature (AT; 20-35°C) and 40°C. Lactic acid production was delayed when stored at 10°C, and acid production stagnated after 2 weeks when stored at 40°C. The patterns of acetic acid and ethanol production were inversely related, with ethanol production promoted at 10°C and 25°C and acetic acid production promoted at AT and 40°C. The bacterial diversity was reduced in TMR silage with high lactic acid and acetic acid content, and the fungal diversity was reduced in TMR silage with high ethanol content. The intensity of lactic acid production was accounted for by the high abundance of Lactobacillus, and its stagnated production at a substantially high storage temperature was related to an increased abundance of Bacillus. The enhanced production of acetic acid or ethanol can be explained by differences in the fungal microbiota. The integrated analysis of bacterial and fungal microbiota can provide in-depth insights into the impact of storage temperature on TMR silage fermentation.

Plasma Short-Chain Fatty Acid (SCFA) Concentrations Are Related to Cognition and Adipose Tissue Mass but Not Muscle Function in Older Adults

ObjectivesShort-chain fatty acids (SCFA) are considered beneficial for overall health and daily functioning but large human trials investigating the relationship between SCFA concentrations and peripheral parameters are scarce. We now tested in a large scale study whether SCFA concentrations correlate to cognitive function, psychological well-being, muscle function, and body composition. MethodsWe selected 232 participants > 50 y from the MEDIT database consisting of healthy adults and adults with ≥1 stable chronic disease. We measured postabsorptive plasma SCFA concentrations (acetate (C2), propionate (C3), butyrate (C4), valerate (C5), isovalerate (Ci5)) by GC-MS and body composition (DXA), respiratory muscle strength (mouth pressure device), handgrip and leg muscle strength and endurance (dynamometry). We assessed cognitive function and severity of depressive symptoms by questionnaires and performed stats by ANCOVA (covariates age, sex, BMI, presence of comorbidity) with significance level P < 0.05. ResultsC2 was the main SCFA correlating with cognitive function tests. A higher C2 concentration was associated with a lower depression score (P = 0.040) and emotional distress (P = 0.018), higher semantic (P = 0.002) and phonemic (P < 0.0001) fluencies, as well as higher mental flexibility (P = 0.054) and selective attention (P = 0.012). In contrast, an elevated C3 concentration was related to higher emotional distress (P = 0.045) and reduced phonemic fluency (P = 0.015), and a higher Ci5 concentration correlated with a lower categorical fluency (P = 0.045). Low C2 (P = 0.027) and high Ci5 (P = 0.004) and C5 (P = 0.008) concentrations correlated with high visceral adipose tissue mass and high C5 concentration with high total fat mass. None of the SCFA concentrations were associated with lean mass, bone mineral density, or muscle function parameters (all P > 0.05). ConclusionsAs the dominant SCFA in the systemic circulation, acetate appears to be crucial for cognitive functioning and emotional well-being. In contrast, high isovalerate and valerate concentrations (products of colonic bacterial amino acid fermentation) are negatively associated with health. Hence, the role of the different SCFA on health is diverse and should be considered separately. Funding SourcesNone

Dietary Fibers: Effects, Underlying Mechanisms and Possible Role in Allergic Asthma Management

The prevalence of asthma is increasing, but the cause remains under debate. Research currently focuses on environmental and dietary factors that may impact the gut-lung axis. Dietary fibers are considered to play a crucial role in supporting diversity and activity of the microbiome, as well as immune homeostasis in the gut and lung. This review discusses the current state of knowledge on how dietary fibers and their bacterial fermentation products may affect the pathophysiology of allergic asthma. Moreover, the impact of dietary fibers on early type 2 asthma management, as shown in both pre-clinical and clinical studies, is described. Short-chain fatty acids, fiber metabolites, modulate host immunity and might reduce the risk of allergic asthma development. Underlying mechanisms include G protein-coupled receptor activation and histone deacetylase inhibition. These results are supported by studies in mice, children and adults with allergic asthma. Fibers might also exert direct effects on the immune system via yet to be elucidated mechanisms. However, the effects of specific types of fiber, dosages, duration of treatment, and combination with probiotics, need to be explored. There is an urgent need to further valorize the potential of specific dietary fibers in prevention and treatment of allergic asthma by conducting more large-scale dietary intervention trials.

Potential Association Between Dietary Fibre and Humoral Response to the Seasonal Influenza Vaccine.

Influenza vaccination is an effective public health measure to reduce the risk of influenza illness, particularly when the vaccine is well matched to circulating strains. Notwithstanding, the efficacy of influenza vaccination varies greatly among vaccinees due to largely unknown immunological determinants, thereby dampening population-wide protection. Here, we report that dietary fibre may play a significant role in humoral vaccine responses. We found dietary fibre intake and the abundance of fibre-fermenting intestinal bacteria to be positively correlated with humoral influenza vaccine-specific immune responses in human vaccinees, albeit without reaching statistical significance. Importantly, this correlation was largely driven by first-time vaccinees; prior influenza vaccination negatively correlated with vaccine immunogenicity. In support of these observations, dietary fibre consumption significantly enhanced humoral influenza vaccine responses in mice, where the effect was mechanistically linked to short-chain fatty acids, the bacterial fermentation product of dietary fibre. Overall, these findings may bear significant importance for emerging infectious agents, such as COVID-19, and associated de novo vaccinations.

The role of short-chain fatty acids in inflammatory bowel diseases and colorectal cancer

Short-chain fatty acids (SCFAs) produced in the human colon are the major products of bacterial fermentation and are believed that they have a protective effect in case of gastrointestinal diseases. SCFAs, such as acetate, propionate, and butyrate are significant metabolites in intestinal homeostasis, and have been shown to be beneficial in inflammatory bowel diseases and colorectal cancer. SCFA are responsible for maintaining proper intestinal barrier and they take part in relevant immune functions. Action of SCFAs is dependent on the activation of protein receptors for receptor activation (GPCR) such as GPR41, GPR43 and GPR109A. In this review, we discuss the effects of SCFA on the intestinal mucosa in terms of inflammatory diseases and colorectal cancer.

Controllers of cutaneous regulatory Tcells: ultraviolet radiation and the skin microbiome.

For the maintenance of homeostasis termination of immune reactions is as equally important as their induction. In this scenario regulatory Tcells (Treg) play an important role. Accordingly a variety of inflammatory diseases are caused by an impairment of Treg. Hence, it is important to identify triggers by which Treg can be induced and activated, respectively. For quite a long time it is known that ultraviolet radiation can induce Treg which inhibit cutaneous immune reactions including contact hypersensitivity. Since these Treg inhibit in an antigen-specific fashion they may harbor therapeutic potential. However similar Treg can be induced also by other triggers which include vitamin D and antimicrobial peptides. Recently it was discovered that the gut microbiome controls the development of Treg in the intestine. The same may apply for the skin. Short chain fatty acids, microbiota-derived bacterial fermentation products, appear to induce and to activate Treg in the skin. Topical application of short chain fatty acids was shown to inhibit contact hypersensitivity and to reduce inflammation inthe murine imiquimod-induced psoriasis-like skin inflammation model. Together, these data indicate that induction and activation of Treg may be a potential therapeutic strategy to treat inflammatory diseases in the future.

Spinosad combined with entomopathogenic nematode for biocontrol of the Mediterranean fruit fly (Ceratitis capitata [Wiedemann]) on citrus

BackgroundCultivation of citrus (Sapindales: Rutaceae) crops is continuously expanding in Egypt given the favorable ingredients of citriculture. Notwithstanding the Egyptian rank as the world's largest orange exporter, the Mediterranean fruit fly (Medfly), Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), is one of the major pests that considerably reduces the quality of citrus crops. Contrary to hazardous organophosphate insecticides that are commonly used to control the Medfly, biologically-based C. capitata control tactics were tried herein. The effect of spinosad as a bacterial fermentation product and the nematode Steinernema riobrave as biological insecticides applied singly or in combination on laboratory and field strains of Medfly were investigated.ResultsA significant difference in LC50 values was observed between laboratory strain (4.78 PPM) and field strain (8.12 PPM) of C. capitata larvae exposed to spinosad. A 1.7 fold decrease in susceptibility of field strain was recorded after treatment with spinosad. In a field experiment, a reduction in Medfly population by 80, 37, and 92% for spinosad, S. riobrave, and spinosad + nematode treatments was recorded, respectively.ConclusionsUtilization of spinosad-S. riobrave combination in citrus fields, as a novel alternative for unhealthy chemical insecticides to control C. capitata in Egypt can be suggested. Use of this combination should be incorporated into a holistic management package that can be economically feasible and environmentally sustainable for Egyptian agriculture.

898-P: Colonic Acetate Production in Youth with and without Obesity

Recent studies suggest that gut microbiota can modulate body weight via products of bacterial fermentation. We tested the hypothesis that, for the same amount of fermentable carbohydrate, lean and obese youth have a different capability to produce acetate in the colon. We also tested the effect of colonic fermentation on plasma glucose, insulin, C-peptide, and free fatty acids (FFA). 38 youth, ages 15 to 21 yr (19 lean/19 obese) underwent a 10-hour sodium [d3]-acetate intravenous infusion to determine the rate of appearance of acetate (Ra) in plasma before and after 20g of lactulose (per os). Pre- and post- Ra values were determined at a quasi-steady state. Compared to obese youth, lean showed a larger increase in Ra after colonic fermentation (P=0.001). Plasma FFA concentrations declined from 0 to 300 minutes (nadir), with a greater reduction in lean youth (P=0.042). Insulin, glucose, and C-peptide levels were lower at the end of the study than at baseline in both groups (all P 0.05). These data suggest that 1) obese youth either ferment lactulose to a lesser degree or experience a higher hepatic uptake of acetate; 2) acetate may cause a reduction in FFA during the fasting state that is more marked in lean youth; 3) acetate may be associated with changes in glucose metabolism, although herein, it is difficult to differentiate between the effect of acetate infusion and prolonged fasting. Disclosure B. Galuppo: None. G. Cline: None. M. A. Van name: None. C. Agazzi: None. C. L. Kien: None. N. Santoro: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK114504)

Implications of SCFAs on the Parameters of the Lipid and Hepatic Profile in Pregnant Women.

Short-chain fatty acids (SCFAs) are the product of the anaerobic intestinal bacterial fermentation of dietary fiber and resistant starch. An abnormal intestinal microbiota may cause a reduction in the production of SCFAs, which stimulate the development of intestinal epithelial cells, nourish enterocytes, influence their maturation and proper differentiation, reduce the pH, and are an additional source of energy for the host. There have been reports of the special role of SCFAs in the regulation of glucose and lipid metabolism during pregnancy. Aim: The aim of the study was to analyze the correlation of SCFAs with lipid and hepatic metabolism during pregnancy in relation to the body weight of pregnant women. Material and methods: This study was conducted in pregnant women divided into two groups: Obese (OW—overweight and obese women; n = 48) and lean (CG—control group; n = 48) individuals. The biochemical plasma parameters of lipid metabolism (TG, CH, LDL, HDL), inflammation (CRP), and liver function (ALT, AST, GGT) were determined in all of the subjects. SCFA analysis was performed in the stool samples to measure acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0 i), butyric acid (C 4:0 n), isovaleric acid (C 5:0 i) valeric acid (C 5:0 n), isocaproic acid (C 6:0 i), caproic acid (C 6:0 n), and heptanoic acid (C 7:0). Results: Statistically significant differences in the concentrations of C 3:0 and C 6:0 n were found between women in the OW group compared to the CG group. The other SCFAs tested did not differ significantly depending on BMI. The C 2:0, C 3:0, and C 4:0 n ratios showed differences in both OW and CG groups. In the OW group, no relationship was observed between the concentrations of the SCFAs tested and CRP, ALT, AST. A surprising positive relationship between C 5:0 n and all fractions of the tested lipids and branched C 5:0 with CHL, HDL, and LDL was demonstrated. In the OW group, HDL showed a positive correlation with C 3:0. However, lower GGT concentrations were accompanied by higher C 4:0 and C 5:0 values, and this tendency was statistically significant. Conclusions: The results of our research show that some SCFAs are associated with hepatic lipid metabolism and CRP concentrations, which may vary with gestational weight. Obesity in pregnancy reduces the amount of SCFAs in the stool, and a decrease in the level of butyrate reduces liver function.

I ncreased Host Energy Metabolism in the Proximal Colon‐Microbiota Interface Elevates Blood Pressure

Introduction : Hypertensive subjects present with alterations in gut microbiota and short chain fatty acids (SCFAs). SCFAs are the major metabolic products of bacterial fermentation in the intestine. While acetate and propionate are energy sources for peripheral tissues, butyrate is the primary energy source for the host colonic epithelium via β-oxidation or glycolysis. Since butyrate is known to elevate blood pressure (BP), we hypothesized that the mechanism of gut microbial butyrate-mediated elevation in BP is linked with an increased energy metabolism in the proximal colon. Methods : To test this hypothesis, 7 weeks old concomitantly raised male germ-free Sprague Dawley rats (GF, n=5-6) were compared with GF acquiring microbiota acutely for 10 days (germ-free conventionalized rats, GFC, n=6) for (1) BP, (2) cecal butyrate by proton nuclear magnetic resonance (1-H NMR), (3) microbial profiling by 16S RNA sequencing and (4) proximal colonic transcriptomic signatures for energy metabolism by real time qRT-PCR. Results : GFC rats acquired microbiota successfully (Figure 1 C and D) and represented an energy-repleted state with a marked increase of the colonic energy substrate, butyrate (Figure 1E). Interestingly, GFC rats had a significant increase in systolic and diastolic BP compared to GF rats (Figure 1 A and B, p<0.05). This increase in BP was associated with a significant upregulation of all 11 genes tested by qRT-PCR for energy metabolism pathways for β-oxidation and glycolysis in the colon of the GFC rats compared to GF rats (Figure 1F). These genes are: peroxisome proliferator activated receptor γ (Pparγ), free fatty acid receptor 2 (Ffar2), acyl-CoA synthetase short chain family member 1(Acss1), acyl-CoA dehydrogenase long chain(Acadl), carnitine palmitoyltransferase 2(Cpt2), hexokinase 2(Hk2), phosphofructokinase, platelet(Pfkp), phosphoglycerate mutase 1(Pgam1), glycerol-3-phosphate dehydrogenase 2(Gpd2), sirtuin 3(Sirt3)and carnitine O-acetyltransferase(Crat). Conclusion : Collectively our data reported here is the first to provide evidence for a direct relationship between host energy metabolism at the proximal gut-microbiota interface and BP regulation. Further, our studies suggest that butyrate, which is a predominant colonic energy metabolite, contributes to the mechanism governing this relationship between energy metabolism in the proximal colon with BP regulation.