Levels Of Total Short-chain Fatty Acids Research Articles

Beneficial Effects of Micronutrient Supplementation in Restoring the Altered Microbiota and Gut-Retina Axis in Patients with Neovascular Age-Related Macular Degeneration-A Randomized Clinical Trial.

Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly and is characterized by a multifactorial etiology. Emerging evidence points to the potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. This study aims to investigate the effects of some micronutrients (such as lutein and zeaxanthin) and saffron (as a supplement)-known for their anti-inflammatory properties-on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Methods: Thirty naive nAMD patients were randomized to receive daily micronutrient supplementation alongside anti-VEGF (vascular endothelial growth factor) therapy, or anti-VEGF treatment alone, over a 6-month period, with comparisons made to a healthy control (HC) group (N = 15). Ophthalmological assessments, biochemical measurements, and stool samples were obtained before and after treatment. Gut microbiota (GM) characterization was performed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and long-chain fatty acids (LCFAs) were analyzed with a gas chromatography-mass spectrometry protocol. Results: Compared to HC, nAMD patients exhibited reduced GM alpha diversity, altered taxonomic composition, and decreased total SCFA levels, in addition to elevated levels of proinflammatory octanoic and nonanoic acids. Micronutrient supplementation was associated with improved visual acuity relative to the group treated with anti-VEGF alone, along with a decrease in the total amount of MCFAs, which are metabolites known to have adverse ocular effects. Conclusions: In conclusion, despite certain limitations-such as the limited sample size and the low taxonomic resolution of 16S rRNA sequencing-this study highlights compositional and functional imbalances in the GM of nAMD patients and demonstrates that micronutrient supplementation may help restore the gut-retina axis. These findings suggest the therapeutic potential of micronutrients in enhancing ocular outcomes for nAMD patients, underscoring the complex interaction between GM and ocular health.

Psidium guajava Seed Oil Reduces the Severity of Colitis Induced by Dextran Sulfate Sodium by Modulating the Intestinal Microbiota and Restoring the Intestinal Barrier.

The oil derived from Psidium guajava seeds (TKSO) exhibits an abundance of diverse unsaturated fatty acids, notably oleic, linoleic, and α-linolenic acids, conferring substantial health advantages in addressing metabolic irregularities and human diseases. This research endeavor focused on elucidating the impacts of TKSO on colonic inflammatory responses and intestinal microbiota alterations in a murine model of colitis induced by dextran sulfate sodium (DSS), demonstrated that substantial supplementation with TKSO reduces the severity of colitis induced by DSS. Furthermore, TKSO effectively attenuated the abundance and expression of proinflammatory mediators while augmenting the expression of tight junction proteins in DSS-challenged mice. Beyond this, TKSO intervention modulated the intestinal microbial composition in DSS-induced colitis mice, specifically by enhancing the relative presence of Lactobacillus, Norank_f_Muribaculaceae, and Lachnospiraceae_NK4A136_group, while concurrently diminishing the abundance of Turicibacter. Additionally, an analysis of short-chain fatty acids (SCFAs) revealed noteworthy elevations in acetic, propionic, isobutyric, and butyric acids, and total SCFAs levels in TKSO-treated mice. In summary, these findings underscore the potential of TKSO to reduce the severity of colitis induced by DSS in mice through intricate modulation of the intestinal microbiota, metabolite profiles, and intestinal barrier repair, thereby presenting a promising avenue for the development of therapeutic strategies against intestinal inflammatory conditions.

Enzymolytic soybean meal-impact on growth performance, nutrient digestibility, antioxidative capacity, and intestinal health of weaned piglets.

Enzymolytic soybean meal (ESBM) enriches free amino acids and small peptides, while mitigating anti-nutritional factors. Substituting soybean meal with ESBM enhances animal performance, though optimal piglet dietary supplementation levels vary. The present study aimed to assess the impact of ESBM on the growth performance, nutrient digestibility, antioxidative capacity and intestinal health of weaned piglets. A total of 120 piglets (initial body weight, 7.0 ± 0.4 kg) were randomly allocated into 4 dietary groups, each comprising 5 replicates with 6 piglets per replicate. The control group received the basal diet, while the experimental groups were fed diets containing 2, 4% or 8% ESBM as a replacement for soybean meal over 28 days. Compared with the control group, piglets supplemented with 4% ESBM exhibited a significant increase (p < 0.05) in average daily gain and the apparent total tract digestibility of dry matter, ether extract and gross energy (p < 0.05), alongside a notable decrease (p < 0.05) in diarrhea incidence. Fed ESBM linearly increased (p < 0.05) the villus height in the ileum of piglets. The levels of superoxide dismutase and total antioxidant capacity in serum of piglets increased (p < 0.05) in the 2 and 4% ESBM groups, while diamine oxidase content decreased (p < 0.05) in the 4 and 8% ESBM group. ESBM inclusion also upregulated (p < 0.05) the expression of superoxide dismutase 1 (SOD-1), Catalase (CAT) and claudin-1 mRNA. In terms of cecal fermentation characteristics, ESBM supplementation resulted in a increase (p < 0.05) in valerate content and a linear rise (p < 0.05) in propionate, butyrate, and total short-chain fatty acids levels, accompanied by a decrease (p < 0.05) in the concentrations of tryptamine and NH3 in cecal digesta. ESBM had no discernible effect on cecal microbial composition. In summary, substitution of soybean meal with ESBM effectively improved the growth performance of piglets by enhancing nutrient digestibility, antioxidant capacity, intestinal barrier and cecal microbial fermentation characteristics, with the optimal replacement level identified at 4%.

Erchen Decoction alleviates obesity-related hepatic steatosis via modulating gut microbiota-drived butyric acid contents and promoting fatty acid β-oxidation

Ethnopharmacological relevanceErchen decoction (ECD) is a traditional Chinese medicine formula comprising six distinct herbs and has been documented to possess a protective effect against obesity. The study conducted previously demonstrated that ECD has the potential to effectively modulate the composition of gut microbiota and levels of short-chain fatty acids (SCFAs) in obese rat. However, the regulatory mechanism of ECD on gut microbiota and SCFAs and further improvement of obesity have not been thoroughly explained. Aim of the studyThe objective of this study was to examine the therapeutic effect and molecular mechanism of ECD in a rat model of high-fat diet (HFD) feeding. Materials and methodsRats with HFD-induced obesity were treated with ECD. Upon completion of the study, serum and liver samples were procured to conduct biochemical, pathological, and Western blotting analyses. The investigation of alterations in the gut microbiota subsequent to ECD treatment was conducted through the utilization of 16S rRNA sequencing. The metabolic alterations in the cecal contents were examined through the utilization of mass spectrometry-ultraperformance liquid chromatography. ResultsECD treatment improved lipid metabolic disorders and reduced hepatic steatosis in HFD-induced obese rats. Obese rat treated with ECD showed a higher abundance of SCFA-producing bacteria, including Lactobacillus, Bifidobacterium, and Butyricicoccus, and lower abundance of disease-related bacteria, such as Bacteroides, Parabacteroides, and Sediminibacterium. Additionally, ECD caused an increase in total SCFAs levels; in particular, butyric acid was dramatically increased in the HFD group. Rats treated with ECD also exhibited significantly increased butyric acid concentrations in the serum and liver. The subsequent reduction in histone deacetylase 1 expression and increase in acetyl-histone 3-lysine 9 (H3K9ac) levels contributed to the promotion of fatty acid β-oxidation (FAO) in liver by ECD. ConclusionThis study demonstrates that ECD regulates the gut microbiota and promotes butyric acid production to ameliorate obesity-related hepatic steatosis. The mechanism might be related to the promotion of FAO via a butyric acid–mediated increase in H3K9ac levels in the liver.

The lipid-lowering effects of fenugreek gum, hawthorn pectin, and burdock inulin.

The present study aimed to investigate the lipid-lowering effects and mechanisms of fenugreek gum (FG), hawthorn pectin (HP), and burdock inulin (BI) on high-fat diet (HFD)-induced hyperlipidemic rats. In this study, high-fat diet (HFD) together with fat emulsion administration were used to establish hyperlipidemia model. The biochemical indices were assayed after administration of FG, HP, and BI. Their effects were evaluated by factor analysis. Alterations of gut microbiota and short chain fatty acids (SCFAs) in the cecal were assessed to illustrate the mechanism of lipid lowering. The supplementation of FG, HP, and BI on HFD-fed rats decreased the levels of serum lipid and reduced the HFD-related liver and testicle damage. In the scatter plot of factor analysis, HP and BI were closer to normal fat diet (NFD) group in restoring the severity of hyperlipidemia, while FG and HP enhanced the excretion of cholesterol and bile acids (BAs). The levels of total SCFAs, especially butyric acid reduced by HFD were increased by HP. The ratio of Firmicutes to Bacteroidetes increased by HFD was reduced by HP and BI. FG, HP, and BI enriched intestinal probiotics, which were related to bile acid excretion or lipid-lowering. FG inhibited the absorption of cholesterol and enhanced the excretion of it, as well as increased the abundance of beneficial bacteria. While BI restored the imbalance of intestinal microbiota. HP enhanced the excretion of cholesterol and BAs, and restored the imbalance of intestinal microbiota. It was also utilized by intestinal microorganisms to yield SCFAs. This study suggested that FG, HP, and BI possessed the potential to be utilized as dietary supplements for obesity management.

Metabolome, microbiome, and gene expression alterations in the colon of newborn piglets with intrauterine growth restriction.

Newborn animals with intrauterine growth restriction (IUGR) are characterized by impaired intestinal structure and function; however, their intestinal microbiota and metabolome profiles have not been fully identified. The present study investigated the differences in colonic microbiota, metabolomics, and barrier function-related gene expression profiles between the IUGR and normal birth weight (NBW) piglets at 7, 21, and 28 days of age. Forty-eight piglets (24 NBW and 24 IUGR) from 24 litters were assigned to assess the differences in colonic microbiota, metabolomics, and gene expression between IUGR and NBW piglets. Compared with the NBW piglets, IUGR piglets showed decreased Shannon index and increased Simpson index at 7 days of age and Chao1 index at 21 days of age (p < 0.05). The IUGR piglets had lower abundances of Firmicutes, Subdoligranulum, Ruminococcaceae_UCG-002, and Ruminococcaceae_UCG-003 at 7 days of age, and Bacteroidetes, Phascolarctobacterium, and Ruminococcaceae_UCG-005 at 21 days of age, when compared with the NBW piglets (p < 0.05). Metabolomics analysis showed significant changes in 147 metabolites mainly involved in organic acids and their derivatives in the colon. Six differential metabolic pathways were significantly enriched, including purine metabolism, amino sugar/nucleotide sugar metabolism, ubiquinone/other terpenoid-quinone biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, phenylalanine metabolism, and histidine metabolism. Spearman’s correlation analysis further demonstrated significant correlations between colonic microbiota and metabolites. In addition, colonic isobutyrate at 7 days of age, isovalerate and total short-chain fatty acids (SCFAs) at 21 days of age, and acetate, propionate, butyrate, and total SCFAs levels at 28 days of age were lower and isovalerate was higher at 28 days of age in the IUGR piglets than in the NBW piglets (p < 0.05). Furthermore, the mRNA expression of zonula occludens (ZO)-1 at 7 days of age, ZO-1, occludin, and interleukin (IL)-4 at 21 days of age were down-regulated in the IUGR piglets, whereas tumor necrosis factor (TNF)-α and nuclear factor-kappa B (NF-κB) at 28 days of age were up-regulated, when compared with the NBW piglets (p < 0.05). The findings suggest that the IUGR pigs present abnormal microbiota and nutrient metabolism in the colon, which may further affect the intestine barrier function by regulating gene expressions.

Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats.

BackgroundThe brain development of preterm infants is easily affected by various adverse extrauterine factors and complications, resulting in abnormal neurological and cognitive development. Recent studies have found that there is a significant correlation between intestinal microbial changes and cognitive behavior. Nevertheless, the correlation between the cognitive impairment and abnormal changes of intestinal microflora in the preterm newborn has been rarely elucidated.AimTo analyze the differences of fecal intestinal flora, short chain fatty acids (SCFAs) and microbiota-gut-brain axis (MGBA)-related serum factors between preterm birth with and without cognitive impairment.MethodsHealthy female rats (body weight 410 ± 40 g) of 16-17 days of gestation were selected for the establishment of preterm cognitive impairment model and screened by Morris water maze navigation experiments. The pathological change of rat hippocampus was confirmed by HE staining. The abundance of fecal intestinal microflora was determined by 16sRNA sequencing, while the contents of fecal SCFAs were examined by gas chromatography.ResultsCompared with the control group, the cognitive impairment group had decreased abundance and diversity of intestinal microflora and increased abundance of Proteobacteria at the level of phylum. While the abundances of Alistipes, Bacteroides, Prevotella, and Lactobacillus decreased significantly at the level of order, family, and genus, the abundances of Staphylococcaceae, Enterococci, Psychrobacter, and Oligella increased significantly. Moreover, the levels of total SCFAs and acetic acid in the disease group were significantly lower. The fecal abundance of acetic acid was positively correlated with that of Lactobacillaceae or Peptostreptococcaceae, and negatively correlated with that of Aerococcaceae, and Alcaligenaceae in disease rats. Furthermore, cognitive impairment caused significantly decreased levels of 5-HT, GABA, and BDNF, and increased levels of GR, CRH, IL-6, and TNF-α in rat blood.ConclusionAlterations in intestinal microflora structure and the abundances of SCFAs contributed substantially to the cognitive impairment in preterm rats, which was associated with significant changes in MGBA-related soluble factors.

Eurotium cristatum reduces obesity by alleviating gut microbiota dysbiosis and modulating lipid and energy metabolism.

Fuzhuan brick tea (FBT) has been shown to prevent obesity, but little is known about the effect of Eurotium cristatum, a critical fungus from FBT. This study examined the effects of live E. cristatum on lipid metabolism and gut microbiota composition in high-fat (HF) diet-induced obese mice. Male HF diet-fed mice were treated with E. cristatum for 12 weeks. The results showed that E. cristatum administration caused strong inhibition against HF-induced body weight gain, dyslipidemia and liver oxidative stress damage. Additionally, Firmicutes and Bacteroidetes in phylum level and six types of bacterial including short-chain fatty acids (SCFAs) producing bacteria in genus level were found to be significantly changed in E. cristatum treated mice as compared to HF fed mice. As expected, E. cristatum could increase total SCFAs levels in feces. Interestingly, E. cristatum markedly increased the proportion of Akkermansia to resist obesity. Functional prediction analysis indicated that E. cristatum changed lipid and energy metabolism. Furthermore, E. cristatum ingestion can modulate hepatic acetyl-coa carboxylase (ACC), fatty acid synthase (FAS), sterol-regulatory element binding protein-1 (SREBP-1) and adipose uncoupling protein-1 (UCP-1) expression. Conclusively, these findings suggest that E. cristatum can prevent the HF-induced lipid accumulation and other complications by modulating gut microbiota, lipid and energy metabolism. © 2022 Society of Chemical Industry.

The effect of serum lipids and short-chain fatty acids on cognitive functioning in drug-naïve, first episode schizophrenia patients

ObjectiveMany studies have reported the important role of serum levels of short-chain fatty acids (SCFAs) in lipid metabolism and cognitive dysfunction. This study investigated the role of plasma lipids and SCFAs on cognitive functioning in drug- naïve first episode schizophrenia. MethodsThis study recruited 44 schizophrenia inpatients and 35 healthy controls. Plasma lipid metabolism was characterized using standard enzymatic methods and an automated analyzer. Serum levels of SCFAs were measured by Gas chromatography mass spectrometry (GC-MS). Cognitive performance was evaluated by the MATRICS Consensus Cognitive Battery (MCCB). ResultsThe patient group showed significantly higher serum levels of total SCFAs, acetic acid, acetic acid/ propionic acid ratio, and poorer cognitive scores compared with the control group (p's < 0.05). Within the patient group, the lipid levels were positively associated with acetic acid/ propionic acid ratio (p's < 0.05). Furthermore, multiple regression analysis revealed that the interactions of LDL level × acetic acid/ propionic acid ratio was a significant predictor of the MCCB working memory, and processing speed subscale scores within the patient group. ConclusionsCognitive dysfunction and abnormal serum levels of SCFAs occur in the early phase of schizophrenia. Lipid metabolism and serum levels of SCFAs might be, both independently or interactively, associated with cognitive dysfunction in schizophrenia.

Long-term drench of exopolysaccharide from Leuconostoc pseudomesenteroides XG5 protects against type 1 diabetes of NOD mice via stimulating GLP-1 secretion.

Type 1 diabetes is an autoimmune disease that results in the specific destruction of insulin-producing beta cells in the pancreas. The aim of this study was to investigate the mechanism of exopolysaccharide from Leuconostoc pseudomesenteroides XG5 (XG5 EPS) against type 1 diabetes. Long-term drench of XG5 EPS delayed the onset of autoimmune diabetes and had fewer islets with high-grade infiltration (an insulitis score of 3 or 4) than untreated NOD mice. Oral administration of 50 mg kg-1 d-1 XG5 EPS increased the insulin and glucagon-like peptide-1 (GLP-1) levels of serum, stimulated GLP-1 secretion and upregulated gcg mRNA expression of colon in NOD mice. Moreover, oral administration of 50 mg kg-1 d-1 XG5 EPS significantly increased total short-chain fatty acids levels in the colon contents, especially those of acetic acid and butyric acid. In NCI-H716 cells, 500 and 1000 μmol L-1 sodium butyrate promoted the secretion of GLP-1 and upregulated the mRNA expression of gcg and PC3, while XG5 EPS and sodium acetate did not stimulate the GLP-1 secretion. Therefore, long-term drench of XG5 EPS delayed the onset of autoimmune diabetes, which may be directly correlated with the increase of butyrate in the colon of NOD mice. Long-term drench of 50 mg kg-1 d-1 XG5 EPS promoted the expression and secretion of GLP-1 by increasing the production of butyric acid, thereby delaying T1D onset in NOD mice. © 2021 Society of Chemical Industry.

Fecal Short-Chain Fatty Acid Ratios as Related to Gastrointestinal and Depressive Symptoms in Young Adults.

Short-chain fatty acids (SCFAs) are produced by the gut microbiota and may reflect health. Gut symptoms are common in individuals with depressive disorders, and recent data indicate relationships between gut microbiota and psychiatric health. We aimed to investigate potential associations between SCFAs and self-reported depressive and gut symptoms in young adults. Fecal samples from 164 individuals (125 were patients with psychiatric disorders: mean [standard deviation] age = 21.9 [2.6] years, 14% men; 39 nonpsychiatric controls: age = 28.5 [9.5] years, 38% men) were analyzed for the SCFA acetate, butyrate, and propionate by nuclear magnetic resonance spectroscopy. We then compared SCFA ratios with dimensional measures of self-reported depressive and gut symptoms. Depressive symptoms showed a positive association with acetate levels (ρ = 0.235, p = .003) and negative associations with both butyrate (ρ = -0.195, p = .014) and propionate levels (ρ = -0.201, p = .009) in relation to total SCFA levels. Furthermore, symptoms of diarrhea showed positive associations with acetate (ρ = 0.217, p = .010) and negative associations with propionate in relation to total SCFA levels (ρ = 0.229, p = 0-007). Cluster analysis revealed a heterogeneous pattern where shifts in SCFA ratios were observed in individuals with elevated levels of depressive symptoms, elevated levels of gut symptoms, or both. Shifts in SCFAs are associated with both depressive symptoms and gut symptoms in young adults and may have of relevance for treatment.

In vitro evaluation of the anti-pathogenic activity of Okoubaka aubrevillei on the human gastrointestinal tract.

Background Okoubaka aubrevillei is used in traditional West African medicine and in homeopathy for treatment and prevention of several gastrointestinal problems. The aim of this in vitro study was to evaluate the effect of repeated doses of two Okoubaka products (10 % ethanolic tincture, mother tincture (MT); 3 rd decimal potency, 3X) on the microbial activity of physiological human colon microbiota using a Simulator of the Human Intestinal Microbial Ecosystem (SHIME ® ) and to investigate any preventive effect against infections with diarrhea-causing pathogens. Methods Upon inoculation with fecal microbiota from a healthy donor, 4 parallel proximal colon compartments of the SHIME were treated either with Okoubaka MT, Okoubaka 3X, ethanol control or blank control for 7 days. Using the Okoubaka -adapted microbial community from SHIME, 48 h challenge tests were performed with enterotoxigenic Escherichia coli (ETEC) and Salmonella enteritidis in 4 different doses (10 3 –10 8 colony forming units as typical in vivo infectious doses). Pathogen concentrations, short-chain fatty acids (SCFAs) and branched SCFA production were measured in triplicate at 0, 24 and 48 h. Results In the challenge tests, both Okoubaka products were able to restrict the colonization of ETEC and Salmonella at 3 of the 4 pathogen doses (except the highest doses), with a stronger anti-pathogenic effect for MT, which included a reduction of 2.0 log-units of ETEC (p < 0.0001) and 1.1 log-units of Salmonella (p < 0.0001). Total SCFA levels remained unaffected, but butyrate increased during the first 24 h (p < 0.0001 for ETEC), accompanied by decreased acetate production. Conclusion We observed in vitro a systemic activating effect of Okoubaka on intestinal microbiome resistance, which resulted in an anti-pathogenic effect, especially against ETEC. We hypothesize that the mode of action in vivo is also based on systemic regulative effects.

Performance, nutrient digestibility and selected gut health parameters of broilers fed with black soldier fly, lesser mealworm and yellow mealworm

This study aimed to investigate the effect of feeding three types of insect meal on broilers’ performance and selected gut health parameters. Day-old straight-run Ross 308 broilers (n=600) were group housed in 24 pens and fed diets containing 10% of eitherTenebrio molitor (yellow mealworm, YMW), defattedHermetia illucens (black soldier fly, BSF) orAlphitobius diaperinus (lesser mealworm, LMW), or a control (CTRL) diet for 35 days. Feed intake and gain were recorded at days 14, 28 and 35. On day 13, four broilers from each pen were placed in metabolic cages to determine apparent total tract digestibility after adaptation to 100% of one of three types of insect meal. Birds were killed, and intestinal content was collected on days 22 and 36 for determination of pH, selected groups of intestinal bacteria and short chain fatty acids (SCFA). Footpad lesions were scored on day 36. Birds fed LMW and YMW ate less than birds fed BSF or CTRL, but feed conversion ratio (FCR) was improved when birds were fed LMW. Dry matter digestibility was similar among insects, but differences were observed in ash and fat digestibility and nitrogen retention in which the BSF meal gave the highest digestibility of these nutrients. Birds fed any type of insect meal diet had higher levels ofClostridium perfringens in caecal and ileal digesta. Footpad dermatitis severity was similar between CTRL and insect-supplemented diets. Total SCFA levels as well as butyrate in digesta of birds fed BSF was lower than the levels of these SCFA in the other treatments. The propionate concentrations in caecal and ileal digesta were high for all diets containing insect meal. In conclusion, gain was maintained when feeding BSF but not LMW and YMW due to lower feed intake. Insect meal did not affect indicators of broilers’ gut health.

A MULTI-SITE ANALYSIS OF THE HUMAN GUT MICROBIOME AND METABOLITES IN ASSOCIATION WITH AMBULATORY BLOOD PRESSURE

Objective: High blood pressure (HBP) is a major risk factor for cardiovascular disease (CVD) and the prevalence of both is higher in regional versus metropolitan areas. The gut microbiome has emerged as important contributor to HBP, however, the relationship between BP and specific gut microbes and their metabolites is unclear. Here we aimed to determine if specific gut microbes and key metabolites such as short-chain fatty acids (SCFAs) were associated with 24 h BP whether geographic differences exist in Australia. Design and method: We recruited 70 subjects from the community in metropolitan (n = 40) and regional (n = 30) locations in Australia. White coat hypertension was present in 6% and masked hypertension in 19% of the cohort, and 34% were hypertensive. We assessed office and ambulatory BP, dietary intake via food frequency questionnaire, gut metabolites by gas-chromatography, and gut microbiome by 16S sequencing. Results: Mean(±SD) 24 h mean arterial pressure was 90.5 ± 10mmHg, systolic BP 122.8 ± 14.9mmHg, and diastolic 74 ± 8.4mmHg. There was a positive correlation between plasma short-chain fatty acid butyrate and 24 h systolic (r = 0.31, P = 0.01) and diastolic BP (r = 0.29, P = 0.02), confirmed by logistic regressions adjusted for age, sex and BMI (P = 0.001). Fifty seven genus were significantly correlated with diastolic BP (r = 0.38–0.41) after adjustment for multiple comparisons (FDR &lt; 0.1). Inverse Simpson index, a marker of alpha diversity, was negatively correlated with 24 h mean arterial pressure (r = -0.24, P = 0.04), being driven particularly by 24 h diastolic BP and day BP. There were no differences in alpha or beta diversity between metropolitan and regional areas. Participants from metropolitan areas, however, had significantly lower levels of total SCFAs, acetate and butyrate (P &lt; 0.05) without having any differences in fibre intake. Conclusions: This is the first study to analyse BP as a continuous variable, suggesting it is associated with a less diverse gut microbiome, higher levels of butyrate, and several genus of gut bacteria. Further studies will need to determine a causal relationship for these associations. We did not find a gut microbial difference between metropolitan and regional participants, but the latter had lower levels of SCFAs, which could help explain their predisposition to hypertension and cardiovascular disease.

Changes in fecal short-chain fatty acids following fecal microbiota transplantation in patients with irritable bowel syndrome.

BackgroundShort‐chain fatty acids (SCFAs) may play a role in the pathophysiology of irritable bowel syndrome (IBS). This study analyzed fecal SCFAs after performing fecal microbiota transplantation (FMT) in the IBS patients who were included in our previous study of the efficacy of FMT.MethodsThis study included 142 of the 164 IBS patients who participated in our previous study. They were belonging to three groups: placebo (own feces), 30‐g (superdonor feces), and 60‐g (superdonor feces) FMT. The patients completed the IBS Severity Scoring System (IBS‐SSS) Birmingham IBS Symptom, Fatigue Assessment Scale (FAS), the IBS Quality of Life (IBS‐QoL) and Short‐Form Nepean Dyspepsia Index (SF‐NDI) questionnaires and delivered fecal samples at the baseline and 1 month after FMT. The SCFA levels were determined by vacuum distillation followed by gas chromatography.Key ResultsThe fecal butyric acid level was significantly increased after FMT in both the 30‐g and 60‐g groups (both P ≤ 0.001). In the 60‐g group, the levels of total SCFAs and isobutyric, isovaleric, and valeric acids increased after FMT. Butyric acid levels in the responders in both the 30‐g and 60‐g FMT groups were significantly inversely correlated with IBS‐SSS and FAS scores (P = 0.001, r = −0.3 and P = 0.0001. r=‐ 0.3, respectively). There were no differences in the SCFA levels in the placebo group after FMT.Conclusion and InferencesFMT increases the fecal SCFA levels in IBS patients. The increase in the butyric acid level is inversely correlated with symptoms in IBS patients following FMT, suggesting that SCFAs might play a role in the pathophysiology of IBS. www.clini​caltr​ials.gov (NCT03822299).

An appraisal of the gut health modulatory effects of a calf faecal-origin probiotic Lactobacillus salivarius CPN60 using Wistar rats with dextran sulfate sodium-induced colitis.

Probiotics of varied origins are being developed for augmenting the gut health of human and animals. The present study aimed to evaluate the effect of a calf-origin probiotic supplement on the gut health of Wistar rats for both healthy and colitis conditions. Forty-eight rats were randomly distributed into four equal groups. The 42-day study involved feeding basal diet alone (CON) or diet supplemented with the calf-origin Lactobacillus salivarius strain CPN60 (PRO). The third (CONc) and fourth (PROc) groups of rats also received the same dietary treatments (CON and PRO, respectively) but were subjected to dextran sulfate sodium (DSS)-induced colitis after 32 days of feeding. The results of a digestion trial conducted after 5 days of DSS administration revealed no influence of probiotic on the digestibility of nutrients. However, the reduced digestibility of protein and fat seen in the CONc rats was improved in the PROc group. The concentrations of lactate and acetate, propionate and butyrate, as well as total short-chain fatty acids (SCFA), were increased (P < 0.05) in the caecal and colonic digesta upon probiotic supplementation, together with significantly reduced colonic ammonia levels. Furthermore, there were reductions (P < 0.05) in acetate, butyrate and total SCFA levels in the caecal contents as a result of colitis. Probiotic supplementation increased (P < 0.05) lactobacilli and bifidobacteria counts in the colon, whereas clostridia and coliform counts were reduced (P < 0.05). These were reversed by the probiotic supplementation. Dietary supplementation of L. salivarius CPN60 had a positive effect with respect to improving the overall gut health of healthy rats, as well as that of rats exposed to experimental colitis. © 2020 Society of Chemical Industry.

Gut Microbiota Dysbiosis Associated With Altered Production of Short Chain Fatty Acids in Children With Neurodevelopmental Disorders.

While gut microbiota dysbiosis has been linked with autism, its role in the etiology of other neurodevelopmental disorders (NDD) is largely underexplored. To our knowledge this is the first study to evaluate gut microbiota diversity and composition in 36 children from the Republic of Serbia diagnosed with NDD and 28 healthy children. The results revealed an increased incidence of potentially harmful bacteria, closely related to Clostridium species, in the NDD patient group compared to the Control group: Desulfotomaculum guttoideum (P < 0.01), Intestinibacter bartlettii (P < 0.05), and Romboutsia ilealis (P < 0.001). On the other hand, significantly lower diversity of common commensal bacteria in the NDD group of patients was noticed. Enterococcus faecalis (P < 0.05), Enterococcus gallinarum (P < 0.01), Streptococcus pasteurianus (P < 0.05), Lactobacillus rhamnosus (P < 0.01) and Bifidobacteria sp. were detected in lower numbers of patients or were even absent in some NDD patients. In addition, butyrate-producing bacteria Faecalibacterium prausnitzii (P < 0.01), Butyricicoccus pullicaecorum (P < 0.05), and Eubacterium rectale (P = 0.07) were less frequent in the NDD patient group. In line with that, the levels of fecal short chain fatty acids (SCFAs) were determined. Although significant differences in SCFA levels were not detected between NDD patients and the Control group, a positive correlation was noted between number of rDNA amplicons obtained with universal primers and level of propionic acid, as well as a trend for levels of total SCFAs and butyric acid in the Control group. This correlation is lost in the NDD patient group, indicating that NDD patients' microbiota differs from the microbiota of healthy children in the presence or number of strong SCFA-producing bacteria. According to a range-weighted richness index it was observed that microbial diversity was significantly lower in the NDD patient group. Our study reveals that the intestinal microbiota from NDD patients differs from the microbiota of healthy children. It is hypothesized that early life microbiome might have an impact on GI disturbances and accompanied behavioral problems frequently observed in patients with a broad spectrum of NDD.

Oral treatment with Lactobacillus reuteri attenuates depressive-like behaviors and serotonin metabolism alterations induced by chronic social defeat stress

BackgroundAlterations in bidirectional gut–brain interactions are believed to be involved in the pathogenesis of neuropsychiatric diseases. Considering the putative connections among gut microbiota, neural function, and behavior, this study investigated the potential of microbe-induced gut–to–brain signaling to modulate the impact of stress on depressive-like behaviors and serotonin metabolism. MethodsDepression-susceptible mice induced by chronic social defeat stress received oral treatment of either Lactobacillus reuteri 3 (L. reuteri 3) or vehicle for 28 days, and alterations in behavior and serotonin metabolism were assessed. 16S rRNA sequencing and gas chromatograph were employed to analyze the gut microbiota community and short-chain fatty acids (SCFAs). ResultsTreatment with L. reuteri 3 ameliorated depressive-like behaviors, suppressed the increase in the relative abundances of Clostridiales and Adlercreutzia, improved the decrease in abundances of Lactobacillus, Allobaculum, and Sutterella induced by stress, and significantly increased the proportion of Bifidobacterium. L. reuteri 3 reduced the acetate and total SCFAs levels in the depression group. Blood and colon 5-HT were decreased in depressive-like mice but were significantly ameliorated after L. reuteri 3 treatment. Moreover, L. reuteri 3 administration increased the expression of enzymes involved in serotonin biosynthesis but suppressed that of the enzymes involved in tryptophan metabolism along the kynurenine pathway in colon and prefrontal cortex. ConclusionsDespite the complexity of the gut microbiota, exposure to a single microbial strain L. reuteri 3 can protect against depressive-like behaviors induced by chronic social defeat stress. The anti-depressive effects of L. reuteri 3 were associated with improved gut microbiota and serotonin metabolism.

Alterations in bacterial communities, SCFA and biomarkers in an elderly HIV-positive and HIV-negative population in western Mexico

BackgroundThe study of stool microbiota has taken great relevance in the last years, given its role in the maintenance of the intestinal metabolic, physiological, and immunological homeostasis, as well as, its effect over HIV biomarkers levels such as CD4/CD8 ratio, high sensitivity C-Reactive Protein (hs-CRP), related to poor outcomes (rapid progression to AIDS). Several efforts have been made to characterize the gut microbiome. In HIV infection, most of the studies report the presence of a dysbiotic pattern; however, few of them have made an approach in elderly HIV-positive subjects despite the fact that nowadays this subgroup is rising. In this study, we compared the composition of faecal microbiota, Short Chain Fatty Acids (SCFAs), and systemic biomarkers between elderly HIV-positive and HIV-negative subjects.MethodsA cross-sectional study with 18 HIV-negative controls and 20 HIV-positive patients. The quantification of Bacteroidetes, Firmicutes, Proteobacteria, Actinobacteria, Lactobacillus, Enterobacteriaceae, Bifidobacterium, Escherichia coli, Clostridium leptum, Clostridium coccoides was performed in faecal samples by qPCR. The analysis was performed by calculating the ΔCq of each microorganism using 16S rDNA as a reference gene. Faecal SCFAs were measured by HPLC. The hs-CRP and sCD14 were performed by ELISA.ResultsAn increase in the Firmicutes/Bacteroidetes ratio, coupled with a significant increase in the proteobacteria phylum was detected in HIV-positive subjects. In contrast, a decrease in the Clostridium leptum group was observed. Nevertheless, these elderly HIV-positive patients showed higher levels of total SCFAs mainly by an augmented propionic acid values, compared to HIV-negative subjects. Whereas high levels of hs-CRP were positively correlated with sCD14 in the HIV-positive group.ConclusionsAlterations in bacterial communities reveals a dysbiotic state related to an unbalance of faecal SCFAs. Therefore, these intestinal conditions might drive an increase of poor prognostic biomarkers in elderly HIV-positive subjects.

Age-related changes in production of short chain fatty acids by oropharyngeal microbiota in patients without respiratory tract and oral disorders

Rationale: Functional activity of upper respiratory tract and oral microbiota has a high informational potential for diagnostics of infectious disease and for development of preventive measure, which is to be explained by rapid variability and high activity of bacteria in this location. Aim: To determine statistical characteristics of concentrations and ratios of the oropharyngeal short chain fatty acids (SCFA) (i.e., functional activity of oropharyngeal microbiota) depending on age of patients without infectious disorder of upper respiratory tract and oral cavity. Materials and methods: Gas liquid chromatography was used to measure SCFA concentrations in saliva from 683 patients aged from 1 month to 85 years who did not have any infections of respiratory tract and oral cavity. Age intervals with homogenous salivary SCFA levels were determined with constant trends in their means (medians) with one-month accuracy. The resulting parameters for the identified age intervals were compared with Mann-Whitney test at 95% significance level (p &lt; 0.05). Results: There were no significant differences between median total SCFA levels (8.04 [4.85; 14.22] mmol/G) and median acetic acid levels (6.27 [3.79; 11.21] mmol/G) in saliva from patients of all ages from 1 month to 85 years. For all other parameters, from 2 to 3 steps of changes were found that occurred at the age of 4 months and 14 years. After the age of 14, the concentrations of propionic and butyric acid significantly increased, whereas those of valeric and caproic acids, as well as of the branched chain SCFA decreased. Correspondingly, after the age of 14, the mean structural index increased from 0.25 to 0.27 U (p &lt; 0.05). The isoacid index decreased with age in two steps: at the age of 4 months from 1.89 to 1.04 U (p &lt; 0.05) and later at the age of 14 years to 0.74 U (p &lt; 0.05). Conclusion: Salivary SCFA levels become stable at the age of 14. The structural index and the isoacid index are most sensitive to the integral changes in the microbiota composition. Analysis of the results of studies on metabolic functioning of microflora should be based on mathematic modeling and multifactorial statistics in three age intervals: from birth to 4 months of age, from 4 months to 14 years and over 14 years.