Combined dilute alkali and milling process enhances the functionality and gut microbiota fermentability of insoluble corn fiber.

In this study, we developed a process combining dilute alkali (NaOH or NaHCO3) and physical (disk milling and/or ball milling) treatments to improve the functionality and fermentability of corn fiber. The results showed that combining chemical with physical processes greatly improved the functionality and fermentability of corn fiber. Corn fiber treated with NaOH followed by disk milling (NaOH-DM-CF) had the highest water retention (19.5 g/g), water swelling (38.8 mL/g), and oil holding (15.5 g/g) capacities. Moreover, NaOH-DM-CF produced the largest amount (42.9 mM) of short-chain fatty acid (SCFA) during the 24-hr in vitro fermentation using porcine fecal inoculum. In addition, in vitro fermentation of NaOH-DM-CF led to a targeted microbial shifting to Prevotella (genus level), aligning with a higher fraction of propionic acid. The outstanding functionality and fermentability of NaOH-DM-CF were attributed to its thin and loose structure, decreased ester linkages and acetyl groups, and enriched structural carbohydrate exposure.

Measurement of short-chain fatty acids in human plasma by means of fast gas chromatography-mass spectrometry.

A rapid and practicable analytical method for the measurement of short-chain fatty acids (SCFAs) in human plasma was developed. The extraction procedure involved the use of acidified water and methyl tert-butyl ether (MTBE), while the separation and detection of SCFAs, including acetic, propionic, and butyric acids was carried out by using gas chromatography-mass spectrometry (GC-MS) technique. The novelty of the research involves reducing the analysis time (less than 7 min) by using the novel fast GC-MS method. A narrow-bore GC capillary column of dimensions 30 m × 0.25 mm ID × 0.25 µm df with acid-modified poly(ethylene glycol) stationary phase was employed for the chromatographic separation. The signals of target compounds were acquired in selected ion monitoring (SIM) mode monitoring a quantifier ion (Q) and two qualifier ions (q1 and q2). Linearity of the method, limits of detection (LoD) and quantification (LoQ) were evaluated. In detail, regression coefficients of the calibration curves were between 0.9960 and 0.9933; LoDs ranged from 0.02 µM to 0.03 µM, while LoQs from 0.06 µM to 0.10 µM.

Effects of fermented soymilk with Lacticaseibacillus paracasei YIT 9029 on gut microbiota and defecation habits: a randomised, double-blind, placebo-controlled study.

Previous studies have demonstrated that soymilk and Lacticaseibacillus paracasei YIT 9029 (strain Shirota: LcS) each beneficially affect the gut microbiota and defecation habits. To investigate the effects of daily consumption of fermented soymilk containing LcS (FSM), we conducted a randomised, double-blind, placebo-controlled study of 112 healthy Japanese adults with a low faecal Bifidobacterium count. They consumed 100 ml FSM or placebo (unfermented soymilk base) once daily for 4 weeks. Their gut microbiota was analysed by 16S rRNA gene amplicon sequencing and quantitative reverse transcription-polymerase chain reaction (PCR), and faecal short-chain fatty acids (SCFAs) and urinary putrefactive products were assessed during the pre- and post-consumption periods. Defecation habits were examined weekly using a subjective questionnaire. In the post-consumption period, living LcS were not detected in two subjects in the FSM group (n = 57) but were detected in one subject in the SM group (n = 55). The FSM group had a significantly higher number and relative abundance of faecal lactobacilli compared with the placebo group. The relative abundance of Bifidobacterium, alpha-diversity of microbiota, and concentrations of acetate and total SCFAs in faeces were significantly increased in the FSM group, although no significant differences were detected between the groups. The number of defecations and defecation days per week significantly increased in both groups. Subgroup analysis of 109 subjects, excluding 3 with inconsistent LcS detection (2 and 1 subjects in the FSM and SM groups, respectively), revealed that the FSM group (n = 55) had significantly greater increases in faecal acetate concentration compared with the SM group (n = 54) and significant upregulation of pathways related to energy production or glucose metabolism in the gut microbiota. These findings suggest that daily FSM consumption improves the gut microbiota and intestinal environment in healthy adults and may help to maintain health and prevent diseases. Registered at the University Hospital Medical Information Network (UMIN) clinical trials registry under: UMIN 000035612.

Faecal microbiota and fatty acids in feline chronic enteropathy.

BACKGROUND: Feline chronic enteropathy is a set of disorders defined as the presence of clinical signs of gastrointestinal disease for at least three weeks. The most common final diagnoses are inflammatory bowel disease and alimentary small cell lymphoma. The etiopathogenesis of these diseases is incompletely understood; however, it is hypothesised that they involve a combination of factors, including altered composition and/or functionality of the intestinal microbiome. An important factor in the interplay of the microbiome and host is the production of short- and branched-chain fatty acids.  The aim of this study was to evaluate the possible differences in faecal microbiota diversity, composition and fatty acid production between cats suffering from chronic enteropathy and healthy cats. Sixteen cats suffering from chronic enteropathy and fourteen healthy control cats were enrolled in the study. The microbiota compositions of faecal samples were analysed by using next-generation amplicon sequencing of the V3V4 fragment of the 16S rRNA gene. Fatty acids were evaluated by high-performance liquid chromatography. RESULTS: Both the alpha and beta diversities were significantly lower in samples obtained from cats with chronic enteropathy. The relative abundance of the phylum Proteobacteria, orders Lactobacillales and Enterobacterales, family Enteriobacteriaceae and genus Escherichia Shigella were higher in diseased cats, whereas the abundance of the phylum Bacteroidota and order Peptococcales were higher in control cats. The faecal concentrations of short-chain fatty acids were higher in cats with chronic enteropathy, with lower propionate proportions and higher butyrate proportions. CONCLUSION: The study revealed alterations in microbiota compositions and short-chain fatty acid concentration in cats suffering from chronic enteropathy, which is an important finding both for research on the pathogenesis of the disease and for potential therapeutic interventions in the form of faecal microbiota transplantation and/or probiotic supplementation.

Protective effect of plantaricin bio-LP1 bacteriocin on multidrug-resistance Escherichia Coli infection by alleviate the inflammation and modulate of gut-microbiota in BALB/c mice model.

The rapid spread of multidrug-resistant pathogens with the low efficacy of common antibiotics for humans and animals in its clinical therapeutics are a global health concern. Therefore, there is a need to develop new treatment strategies to control them clinically. The study aimed to evaluate the effects of Plantaricin Bio-LP1 bacteriocin produced from Lactiplantibacillus plantarum NWAFU-BIO-BS29 to alleviate the inflammation caused by multidrug-resistance Escherichia Coli (MDR-E. coli) infection in BALB/c mice-model. The focus was given on aspects linked to the mechanism of the immune response. Results indicated that Bio-LP1 had highly promising effects on partially ameliorating MDR-E. coli infection by reducing the inflammatory response through inhibiting the overexpression of proinflammatory-cytokines such as secretion of tumor necrosis factor (TNF-α) and interleukin (IL-6 and IL-ß) and strongly regulated theTLR4 signaling-pathway. Additionally, avoided the villous destruct, colon length shortening, loss of intestinal barrier integrity, and increased disease activity index. Furthermore, significantly increased the relative abundance of beneficial-intestinal-bacteria including Ligilactobacillus, Enterorhabdus, Pervotellaceae, etc. Finally, improved the intestinal mucosal barrier to alleviate the pathological damages and promote the production of short-chain fatty acids (SCFAs) a source of energy for the proliferation. In conclusion, plantaricin Bio-LP1 bacteriocin can be considered a safe alternative to antibiotics against MDR-E. coli-induced intestinal inflammation.

Pretreatment of free nitrous acid combined with calcium hypochlorite for enhancement of hydrogen production in waste activated sludge.

A variety of variables limit the recovery of resources from anaerobic fermentation of waste activated sludge (WAS), hence pretreatment strategies are necessary to be investigated to increase its efficiency. A combination of free nitrous acid (FNA) and calcium hypochlorite [Ca(ClO)2] was employed in this investigation to significantly improve sludge fermentation performance. The yields of cumulative hydrogen for the blank and FNA treatment group were 1.09 ± 0.16 and 7.36 ± 0.21 mL/g VSS, respectively, and 6.59 ± 0.24 [0.03 g Ca(ClO)2/g TSS], 7.75 ± 0.20 (0.06), and 8.58 ± 0.22 (0.09) mL/g VSS for the Ca(ClO)2 groups. The co-treatment greatly boosted hydrogen generation, ranging from 39.97 ± 2.26 to 76.20 ± 4.78 % as compared to the solo treatment. Mechanism analysis demonstrated that the combined treatment disturbed sludge structure and cell membrane permeability even more, which released more organic substrates and enhanced biodegradability of fermentation broth. This paper describes a unique strategy to sludge pretreatment that expands the use of Ca(ClO)2 and FNA in anaerobic fermentation, with implications for sludge disposal and energy recovery.

Characterization of soluble dietary fiber from citrus peels (Citrus unshiu), and its antioxidant capacity and beneficial regulating effect on gut microbiota.

This study aimed to evaluate the physicochemical, structural and functional properties of soluble dietary fiber extracted from citrus peels (Citrus unshiu) by ultrasound-assisted alkaline extraction. Unpurified soluble dietary fiber (CSDF) was compared with purified soluble dietary fiber (PSDF) in terms of composition, molecular weight, physicochemical properties, antioxidant activity, and intestinal regulatory capacity. Results showed that the molecular weight of soluble dietary fiber was >15 kDa, which showed good shear thinning characteristics and belonged to non-Newtonian fluid. The soluble dietary fiber showed good thermal stability under 200 °C. The contents of total sugar, arabinose and sulfate in PSDF were higher than those in CSDF. At the same concentration, PSDF showed stronger free radical scavenging ability. In fermentation model experiments, PSDF promoted the production of propionic acid and increased the abundance of Bacteroides. These findings suggested that soluble dietary fiber extracted by the ultrasound-assisted alkaline extraction has good antioxidant capacity and promotes intestinal health. It has broad development space in the field of functional food ingredients.

The impact of cancer cachexia on gut microbiota composition and short-chain fatty acid metabolism in a murine model.

This study investigates the relationship between cancer cachexia and the gut microbiota, focusing on the influence of cancer on microbial composition. Lewis lung cancer cell allografts were used to induce cachexia in mice, and body and muscle weight changes were monitored. Fecal samples were collected for targeted metabolomic analysis for short chain fatty acids and microbiome analysis. The cachexia group exhibited lower alpha diversity and distinct beta diversity in gut microbiota, compared to the control group. Differential abundance analysis revealed higher Bifidobacterium and Romboutsia, but lower Streptococcus abundance in the cachexia group. Additionally, lower proportions of acetate and butyrate were observed in the cachexia group. The study observed that the impact of cancer cachexia on gut microbiota and their generated metabolites was significant, indicating a host-to-gut microbiota axis. [BMB Reports 2023; 56(7): 404-409].

Associations between fecal short-chain fatty acids, plasma inflammatory cytokines, and dietary markers with depression and anxiety: Post hoc analysis of the ENGAGE-2 pilot trial.

BACKGROUND: The microbiome-gut-brain-axis (MGBA) is emerging as an important mechanistic link between diet and mental health. The role of significant modifiers of the MGBA, including gut microbial metabolites and systemic inflammation, in individuals comorbid with obesity and mental disorders, is under-investigated. OBJECTIVES: This exploratory analysis examined associations among microbial metabolites-fecal SCFAs, plasma inflammatory cytokines, and diet with depression and anxiety scores in adults comorbid with obesity and depression. METHODS: Stool and blood were obtained from a subsample (n = 34) of participants enrolled in an integrated behavioral intervention for weight loss and depression. Pearson partial correlation and multivariate analyses determined associations among changes in fecal SCFAs (propionic, butyric, acetic, and isovaleric acids), plasma cytokines [C-reactive protein, interleukin 1 beta, interleukin 1 receptor antagonist (IL-1RA), interleukin 6, and TNF-α], and 35 dietary markers over 2 mo, and changes in SCL-20 (Depression Symptom Checklist 20-item) and GAD-7 (Generalized Anxiety Disorder 7-Item) scores over 6 mo. RESULTS: Changes in the SCFAs and TNF-α at 2 mo were positively associated (standardized coefficients: 0.06-0.40; 0.03-0.34) with changes in depression and anxiety scores at 6 mo, whereas changes in IL-1RA at 2 mo were inversely associated (standardized coefficients: -0.24; -0.05). After 2 mo, changes in 12 dietary markers, including animal protein, were associated with changes in SCFAs, TNF-α, or IL-1RA at 2 mo (standardized coefficients: -0.27 to 0.20). Changes in 11 dietary markers, including animal protein, at 2 mo were associated with changes in depression or anxiety symptom scores at 6 mo (standardized coefficients: -0.24 to 0.20; -0.16 to 0.15). CONCLUSIONS: Gut microbial metabolites and systemic inflammation may be biomarkers of importance within the MGBA, linking dietary markers, such as animal protein intake, to depression and anxiety for individuals with comorbid obesity. These findings are exploratory and warrant replication.

Quantification of short-chain fatty acids in human stool samples by LC-MS/MS following derivatization with aniline analogues.

The gut microbiome produces a range of short chain fatty acids (SCFA) crucially linked with diet and nutrition, metabolism, gastrointestinal health and homeostasis. SCFA are primarily measured using gas or liquid chromatography-mass spectrometry (LC/MS) after undergoing chemical derivatization. Here we assess the merits of a derivatization protocol using aniline and two aniline analogues (3-phenoxyaniline and 4-(benzyloxy)aniline) for the targeted LC-MS/MS quantification of nine SCFA (acetic, propionic, butyric, valeric, caproic acid, isobutyric, isovaleric, 2-methylbutyric, and 2-ethylbutyric acid). Evaluation of product ion spectra and optimization of MS detection conditions, provided superior detection sensitivity for 3-phenoxyaniline and 4-(benzyloxy)aniline compared to aniline. We developed a facile SCFA derivatization method using 3-phenoxyaniline under mild reaction conditions which allows for the simultaneous quantification of these SCFA in human stool samples in under eleven minutes using multiple reaction monitoring LC-MS/MS. The method was successfully validated and demonstrates intra- and inter-day accuracy (88.5-103% and 86.0-109%) and precision (CV of 0.55-7.00% and 0.33-9.55%) with recoveries (80.1-87.2% for LLOQ, 88.5-93.0% for ULOQ) and carry-over of (2.68-17.9%). Selectivity, stability and matrix effects were also assessed and satisfied validation criteria. Method applicability was demonstrated by analysing SCFA profiles in DNA-stabilized human stool samples from newly diagnosed colorectal cancer patients prior to surgery. The development of this improved method and its compatibility to measure SCFAs from DNA-stabilized stool will facilitate studies investigating the gut microbiome in health and disease.

Microbial Composition and Stool Short Chain Fatty Acid Levels in Fibromyalgia.

BACKGROUND: The present study aimed to evaluate microbial diversity, taxonomic profiles, and fecal short chain fatty acid (SCFA) in female patients with fibromyalgia syndrome (FMS). METHODS: Forty participants (19 patients with FMS and 21 controls) were included in the study, and the diagnosis of FMS was made based on the revised American College of Rheumatology criteria. DNA extraction from fecal samples and 16S rRNA gene sequencing were conducted to estimate microbial composition. To compare alpha diversity, the Shannon index accounting for both evenness and richness, Pielou's evenness, and Faith's phylogenetic diversity (PD) were calculated. Unweighted and weighted UniFrac distances, Jaccard distance, and Bray-Curtis dissimilarity were used to calculate beta diversity. Furthermore, stool metabolites were analyzed using gas chromatography-mass spectrometry, and a generalized regression model was used to compare the SCFA of stools between FMS and healthy controls. RESULTS: Compared with the control, patients with FMS had lower observed OTU (p = 0.048), Shannon's index (p = 0.044), and evenness (p < 0.001). Although patients with FMS had a lower PD than did controls, statistical significance was not reached. We observed significant differences in unweighted (p = 0.007), weighted UniFrac-based diversity (p < 0.005), Jaccard distance (p < 0.001), and Bray-Curtis dissimilarity (p < 0.001) between the two groups. Although the FMS groups showed lower propionate levels compared with those of the control group, only marginal significance was observed (0.82 [0.051] mg/g in FMS vs. 1.16 [0.077] mg/g in the control group, p = 0.069). CONCLUSIONS: The diversity of the microbiome in the FMS group was lower than that in the control group, and the reduced stool propionate levels could be associated with the decreased abundance of propionate-producing bacteria.

Analysis of volatile short-chain fatty acids in the gas phase using secondary electrospray ionization coupled to mass spectrometry.

Quantification of metabolites present within exhaled breath is a major challenge for on-line breath analysis. It is also important for gauging the analytical performance, accuracy, reproducibility, reliability, and stability of the measuring technology. Short-chain fatty acids (SCFAs) are of high interest for nutrition and health. Their quantification enables a deep mechanistic understanding of a wide range of biological processes and metabolic pathways, while their high volatility makes them an attractive target for breath analysis. This article reports, for the first time, the development and testing of a modular, dynamic vapor generator for the qualitative and quantitative analysis of volatile SCFAs in the gaseous phase using a secondary electrospray ionization (SESI) source coupled to a high-resolution mass spectrometer. Representative compounds tested included acetic acid, propionic acid, butyric acid, pentanoic acid and hexanoic acid. Gas-phase experiments were performed both in dry and humid (95% relative humidity) conditions from ppt to low ppb concentrations. The results obtained exhibited excellent linearity within the examined concentration range, low limits of detection and quantification down to the lower ppt area. Mixture effects were also investigated and are presented.

Postoperative Probiotics Administration Attenuates Gastrointestinal Complications and Gut Microbiota Dysbiosis Caused by Chemotherapy in Colorectal Cancer Patients.

The current study aims to evaluate the potential roles of taking probiotics postoperatively in attenuating the gastrointestinal complications and disturbed gut microbiota in colorectal cancer (CRC) patients undergoing chemotherapy. One hundred eligible CRC patients who were treated with radical surgery and needed to receive chemotherapy were recruited. Half of them were randomly assigned to the Probio group to take a probiotic combination from post-operation to the end of the first chemotherapeutic course. The other half of patients taking placebo instead were classified as the Placebo group. Gastrointestinal complications such as nausea, acid reflux, abdominal pain, abdominal distention, constipation, and diarrhea were recorded during chemotherapy. Fecal samples were collected preoperatively and after the first cycle of postoperative chemotherapy for 16S rRNA high-throughput sequencing and short-chain fatty acids (SCFAs) analysis. Results showed that probiotics administration could effectively reduce chemotherapy-induced gastrointestinal complications, particularly in diarrhea (p < 0.01). Additionally, chemotherapy also reduced the bacterial diversity indexes of the gut microbiota in CRC patients, which could be significantly increased by taking probiotics. Moreover, this chemotherapy caused significant changes in the composition of the gut microbiota, as indicated by decreased phylum levels of Firmicutes and increased Bacteroidetes, Proteobacteria, and Verrucomicrobia. In particular, several bacterial genera such as Akkermansia and Clostridium were significantly increased, while Prevotella, Lactobacillus, and Roseburia were decreased (p < 0.05). However, probiotic administration could effectively restore these taxa changes both at the phylum and genus levels, and mildly increase the genus levels of Bifidobacterium, Streptococcus, and Blautia. Furthermore, probiotics could also promote the production of SCFAs, particularly increasing acetate, butyrate, and propionate (p < 0.0001). These results support the beneficial effects of the probiotic interventions as novel alternative or complementary strategies in chemoprevention.

Genetic Predictors for Fecal Propionate and Butyrate-Producing Microbiome Pathway Are Not Associated with Colorectal Cancer Risk: A Mendelian Randomization Analysis.

BACKGROUND: Mechanistic data indicate the benefit of short-chain fatty acids (SCFA) produced by gut microbial fermentation of fiber on colorectal cancer, but direct epidemiologic evidence is limited. A recent study identified SNPs for two SCFA traits (fecal propionate and butyrate-producing microbiome pathway PWY-5022) in Europeans and showed metabolic benefits. METHODS: We conducted a two-sample Mendelian randomization analysis of the genetic instruments for the two SCFA traits (three SNPs for fecal propionate and nine for PWY-5022) in relation to colorectal cancer risk in three large European genetic consortia of 58,131 colorectal cancer cases and 67,347 controls. We estimated the risk of overall colorectal cancer and conducted subgroup analyses by sex, age, and anatomic subsites of colorectal cancer. RESULTS: We did not observe strong evidence for an association of the genetic predictors for fecal propionate levels and the abundance of PWY-5022 with the risk of overall colorectal cancer, colorectal cancer by sex, or early-onset colorectal cancer (diagnosed at <50 years), with no evidence of heterogeneity or pleiotropy. When assessed by tumor subsites, we found weak evidence for an association between PWY-5022 and risk of rectal cancer (OR per 1-SD, 0.95; 95% confidence intervals, 0.91-0.99; P = 0.03) but it did not surpass multiple testing of subgroup analysis. CONCLUSIONS: Genetic instruments for fecal propionate levels and the abundance of PWY-5022 were not associated with colorectal cancer risk. IMPACT: Fecal propionate and PWY-5022 may not have a substantial influence on colorectal cancer risk. Future research is warranted to comprehensively investigate the effects of SCFA-producing bacteria and SCFAs on colorectal cancer risk.

Associative effects between Chlorella vulgaris microalgae and Moringa oleifera leaf silage used at different levels decreased in vitro ruminal greenhouse gas production and altered ruminal fermentation.

Moringa oleifera leaf silage and Chlorella vulgaris microalgae mixture used at different levels replacing concentrate feed mixture in the diets of ruminant were evaluated using an in vitro gas production technique. C. vulgaris was included in rations at 1, 2, and 3% concentrations. The concentrate feed mixture was replaced by M. oleifera silage up to 100%. Productions of total gas, methane (CH4), and carbon dioxide (CO2) and ruminal fermentation were measured. Interactions between M. oleifera and C. vulgaris levels were observed for the rate of total gas production, lag time of CH4 production, pH, and concentrations of ammonia-N (NH3-N), total volatile fatty acid (VFA), and propionate. The lower level of C. vulgaris increased total gas production and decreased CH4 and CO2 production as well as improved nutrient degradability compared to the other levels of C. vulgaris which showed less improvement in these parameters. The replacement levels of concentrate at 10 to 40% with M. oleifera linearly increased the asymptotic total gas production and degradabilities of dry matter and acid detergent fiber (P<0.05), while the replacement levels of 80 to 100% lowered the asymptotic (P<0.01) for the ration containing 1% C. vulgaris. Rations containing M. oleifera linearly increased the lag time of total gas production (P<0.05), neutral detergent fiber degradability, and ruminal bacteria count and decreased the asymptotic CH4 and CO2 production and ruminal protozoal count (P<0.05). For the rations containing 2 and 3% C. vulgaris, M. oleifera linearly (P<0.01) decreased the asymptotic total gas, CH4 and CO2 production, and ruminal protozoal count. The lag time of CH4 production was not affected at 1% C. vulgaris, but reduced linearly at 2% and 3% C. vulgaris. Ruminal pH was not affected by M. oleifera, but was increased by C. vulgaris at 3% level. Overall, M. oleifera in the ration containing C. vulgaris at all levels increased ruminal NH3-N concentration; however, C. vulgaris at 2% level and M. oleifera at levels up to 40% lowered NH3-N concentration. M. oleifera rations with 1% and 2% C. vulgaris increased the concentrations of total VFA and propionate, whereas these variables were not affected at 3% C. vulgaris level. In conclusion, replacement of concentrate mixture with M. oleifera at 30% level and C. vulgaris at 1% in the diet due to associative effects may improve ruminal fermentation and feed degradability while decreasing CH4 production.

Gut microbiota analysis for prediction of clinical relapse in Crohn's disease.

The role of intestinal bacterial microbiota has been described as key in the pathophysiology of Crohn's disease (CD). CD is characterized by frequent relapses after periods of remission which are not entirely understood. In this paper, we investigate whether the heterogeneity in microbiota profiles in CD patients could be a suitable predictor for these relapses. This prospective observational study involved 259 CD patients, in which 41 provided an additional total of 62 consecutive fecal samples, with an average interval of 25 weeks in between each of these samples. Fecal microbiota was analyzed by massive genomic sequencing through 16 S rRNA amplicon sampling. We found that our 259 CD patients could be split into three distinct subgroups of microbiota (G1, G2, G3). From G1 to G3, we noticed a progressive decrease in alpha diversity (p ≤ 0.0001) but no change in the fecal calprotectin (FC) level. Focusing on the 103 consecutive samples from 41 CD patients, we showed that the patients microbiota profiles were remarkably stable over time and associated with increasing symptom severity. Investigating further this microbiota/severity association revealed that the first signs of aggravation are (1) a loss of the main anti-inflammatory Short-Chain Fatty Acids (SCFAs) Roseburia, Eubacterium, Subdoligranumum, Ruminococcus (P < 0.05), (2) an increase in pro-inflammatory pathogens Proteus, Finegoldia (P < 0.05) while (3) an increase of other minor SCFA producers such as Ezakiella, Anaerococcus, Megasphaera, Anaeroglobus, Fenollaria (P < 0.05). Further aggravation of clinical signs is significantly linked to the subsequent loss of these minor SCFAs species and to an increase in other proinflammatory Proteobacteria such as Klebsiella, Pseudomonas, Salmonella, Acinetobacter, Hafnia and proinflammatory Firmicutes such as Staphylococcus, Enterococcus, Streptococcus. (P < 0.05). To our knowledge, this is the first study (1) specifically identifying subgroups of microbiota profiles in CD patients, (2) relating these groups to the evolution of symptoms over time and (3) showing a two-step process in CD symptoms' worsening. This paves the way towards a better understanding of patient-to-patient heterogeneity, as well as providing early warning signals of future aggravation of the symptoms and eventually adapting empirically treatments.

Short-chain fatty acid concentrations in the incidence and risk-stratification of colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: The beneficial role of gut microbiota and bacterial metabolites, including short-chain fatty acids (SCFAs), is well recognized, although the available literature around their role in colorectal cancer (CRC) has been inconsistent. METHODS: We performed a systematic review and meta-analysis to examine the associations of fecal SCFA concentrations to the incidence and risk of CRC. Data extraction through Medline, Embase, and Web of Science was carried out from database conception to June 29, 2022. Predefined inclusion/exclusion criteria led to the selection of 17 case-control and six cross-sectional studies for quality assessment and analyses. Studies were categorized for CRC risk or incidence, and RevMan 5.4 was used to perform the meta-analyses. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model. Studies lacking quantitation were included in qualitative analyses. RESULTS: Combined analysis of acetic, propionic, and butyric acid revealed significantly lower concentrations of these SCFAs in individuals with a high-risk of CRC (SMD = 2.02, 95% CI 0.31 to 3.74, P = 0.02). Additionally, CRC incidence was higher in individuals with lower levels of SCFAs (SMD = 0.45, 95% CI 0.19 to 0.72, P = 0.0009), compared to healthy individuals. Qualitative analyses identified 70.4% of studies reporting significantly lower concentrations of fecal acetic, propionic, butyric acid, or total SCFAs in those at higher risk of CRC, while 66.7% reported significantly lower concentrations of fecal acetic and butyric acid in CRC patients compared to healthy controls. CONCLUSIONS: Overall, lower fecal concentrations of the three major SCFAs are associated with higher risk of CRC and incidence of CRC.

Correlation between altered gut microbiota and elevated inflammation markers in patients with Crohn's disease.

Prior studies reported inconsistent results on the altered gut microbial composition in patients with Crohn's disease (CD), likely under the influences of many confounding factors including genetic, life style and environmental variations among different study cohorts. This study aims to examine the gut microbiota of CD patients with particular efforts to minimize the impact of the confounding factors. For this purpose, the healthy relatives of the patients were enrolled as control subjects so that the paired study subjects may have similar genetic background, dietary habits, and household environment. The fecal microbiota of the study subjects were examined by 16S rRNA sequencing. After the identification of the differential bacterial genera, multivariate regression analysis was performed to adjust the results for the impact of confounding factors. We found that the microbiota of the CD patients were featured with reduced short chain fatty acid (SCFA) producing bacteria and elevated opportunistic pathogen Escherichia-Shigella. Correlation analysis indicated that the elevation in Escherichia-Shigella and the reduction in SCFA-producing bacteria usually occur simultaneously. These differential genera exhibited a high capacity in distinguishing between CD and healthy controls achieving an area under curve of 0.89, and were correlated with the changes in inflammation related blood biochemical markers. Consistent with the reduction in SCFA-producing bacteria in CD, metabolomics analysis revealed decreased blood level of SCFAs in the patients. The differential genera identified in this study demonstrated outstanding capability to serve as diagnosis markers for CD and are potential targets for intervention.

Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial.

BACKGROUND: The Mediterranean diet is associated with the prevention of diabetes, cardiovascular disease, and cancer, all of which are linked to intestinal barrier impairment. OBJECTIVES: Here, we hypothesize that the Mediterranean diet, possibly via the induction of short-chain fatty acids (SCFAs), improves intestinal barrier integrity. Furthermore, we aim to establish novel personalized nutrition advice based on machine learning algorithms. METHODS: We studied 260 women with intestinal barrier impairment. The women were allocated to follow either a Mediterranean diet or a control diet for 3 mo. Intestinal permeability was assessed by measuring lipopolysaccharide binding protein (LBP) in plasma and zonulin in feces. SCFA concentrations were analyzed in feces. Bi- and multivariate analyses and machine learning algorithms (random forest classification) were conducted. RESULTS: Particularly in the intervention group, adherence to the Mediterranean diet increased, whereas plasma LBP and fecal zonulin concentrations decreased (all q < 0.001 for the intervention group, all q < 0.1 for control group). In the intervention group, fecal SCFA concentrations increased (propionate + 19%; butyrate + 44%; both q < 0.001). Multivariate analyses showed that adherence to the Mediterranean diet was associated with SCFA concentrations (all q < 0.001) and inversely associated with LBP and zonulin concentrations (all q < 0.02). Mediation analyses identified propionate and butyrate as the key mechanistic link between diet and intestinal permeability integrity. Accordingly, using baseline SCFA data, we could predict the effect of the Mediterranean diet on intestinal permeability using a machine learning algorithm (receiver operating characteristic AUC: 0.78-0.96). CONCLUSIONS: Our data suggest that SCFAs are key mediators for the relation between diet and gut health. Assessment of SCFAs may form a basis for personalized nutrition in future clinical care. These results need to be verified in larger studies powered for this purpose, comprising different study populations. The trial was registered at clinicaltrials.gov as NCT02087592 and NCT02516540.

Microbiota responses to different prebiotics are conserved within individuals and associated with habitual fiber intake.

BACKGROUND: Short-chain fatty acids (SCFAs) derived from gut bacteria are associated with protective roles in diseases ranging from obesity to colorectal cancers. Intake of microbially accessible dietary fibers (prebiotics) lead to varying effects on SCFA production in human studies, and gut microbial responses to nutritional interventions vary by individual. It is therefore possible that prebiotic therapies will require customizing to individuals. RESULTS: Here, we explored prebiotic personalization by conducting a three-way crossover study of three prebiotic treatments in healthy adults. We found that within individuals, metabolic responses were correlated across the three prebiotics. Individual identity, rather than prebiotic choice, was also the major determinant of SCFA response. Across individuals, prebiotic response was inversely related to basal fecal SCFA concentration, which, in turn, was associated with habitual fiber intake. Experimental measures of gut microbial SCFA production for each participant also negatively correlated with fiber consumption, supporting a model in which individuals' gut microbiota are limited in their overall capacity to produce fecal SCFAs from fiber. CONCLUSIONS: Our findings support developing personalized prebiotic regimens that focus on selecting individuals who stand to benefit, and that such individuals are likely to be deficient in fiber intake. Video Abstract.