Fecal Levels Research Articles

The Crucial Role of Gut Microbiome in Cardiovascular Health

Madam, The intestinal microbiome refers to the vast assortment of tiny organisms in the human digestive tract. These bacteria support the body's physiological processes and biochemical responses via the compounds they generate. Research suggests that variations in gut microbiota may influence a variety of human health disorders, notably those involving the heart. Recent studies have shown that changes in the types and activities of bacteria in the intestines, known as gut microflora dysbiosis, can hasten the course of cardiovascular illnesses 1. Another research also tied gut microbiota to heart disease, but this time by demonstrating how metabolites like trimethylamine N-oxide (TMAO) will increase risk, indicating that dietary and probiotic strategies could be used for remedy 2. A recent study from April 2024 identified Oscillibacter and Eubacterium as synergistic cholesterol metabolisers. The intermediate products that these bacteria form while converting cholesterol are finally degraded by other bacteria and flushed out from the body, reducing gut cholesterol and modulating the host's biochemical pathways, hence reducing both faecal and plasma cholesterol levels. The results may serve to facilitate novel potential interventions, for example targeting the microbiome in cardiovascular disease (CVD) treatment 3. A novel association was observed that higher serum C-reactive protein (CRP) levels correlate with Parabacteroides merdae and unclassified Firmicutes strongly associate with plasma cholesterol. As for Firmicutes a well-defined metagenomic species pangenome (MSP) from this phylum, termed msp_120, was found to be associated with higher cholesterol levels that indicate its role in cholesterol metabolism and thus possibly also as a determinant of cardiovascular disease risk factors concerning high serum-cholesterol level. This finding reveals a beholden link between the gut microbiome and systemic inflammation with CVD 3. In Pakistan, where CVDs are a major health concern, there is a significant research gap regarding the local gut microbiome's role in CVD. We conducted thorough research on PubMed and found no original research articles studying the relationship of gut microbiome with CVD except for a few review articles 4 and 5; this is indicative of the lack of attention to this topic in Pakistan. It is important to perform ethnic-specific studies for these unique interactions in the Pakistani population. Research in this direction may point out the specific role of gut microbiota so probiotic interventions and dietary recommendations can be used to improve cardiovascular health in the Pakistani population.

Elevated Fecal Lipocalin-2 Levels During Early Life Are Associated with Maternal Inflammatory Bowel Disease Diagnosis.

Fecal lipocalin-2 (LCN2) is a biomarker of neutrophil activation, which is elevated in patients with inflammatory bowel disease (IBD); however, its dynamic changes during pregnancy and early life are largely unknown. We characterized LCN2 levels by maternal IBD diagnosis, offspring feeding behavior, and gut microbiota composition. In the prospective MECONIUM (Exploring Mechanisms of Disease Transmission In Utero through the Microbiome) study, we analyzed 559 fecal samples from 91 pregnant women with IBD, 78 healthy controls, and their 147 offspring for LCN2 levels at each trimester of pregnancy and multiple time points during early life using linear mixed-effects model and multiple logistic regression analyses. Gut microbiota community compositions were evaluated following 16S rRNA gene sequencing. IBD cases had higher LCN2 levels throughout pregnancy compared to controls. In offspring, significantly higher LCN2 was found in babies born to mothers with IBD, compared to those without IBD, at 3months, 1year, and 4years (all p < 0.03), with offspring LCN2 levels being predictive of maternal IBD case status with > 85% accuracy at ages 1 and 4. We also detected correlations between LCN2 levels and certain IBD-associated bacterial taxa in both mothers and babies. Exclusively breastfed babies had lower LCN2 in the first weeks of life compared to formula or mixed-fed counterparts. Babies born to mother with IBD had significantly higher LCN2 during early life compared to controls with exclusive breastfeeding impacting LCN2 levels early on. LCN2 levels correlated with IBD-associated microbial taxa in both mothers and babies. Future studies should identify the biological drivers and health-related consequences of elevated LCN2 during early childhood.

A multidimensional fecal microbial and inflammatory biomarker profiling in preterm and full-term neonates.

Preterm birth affects approximately one in every ten neonates. The clinical outcomes depend on care and management factors, including the birth delivery method and the use of antibiotics. This observational cohort study determined antimicrobial peptides, proteases, metabolomic, and microbiome profiles in fecal samples collected from 20 preterm and nine full-term neonates 48 h after birth. The results show that preterm neonates have increased levels of α-defensins, serine proteases, and matrix metalloproteinases. They also have distinct metabolic signatures characterized by decreased kynurenic acid and increased mevalonate levels. These neonates also exhibit reduced microbial diversity. This study highlights that heightened immune response and proteolytic activity, marked dysbiosis, and reduced short-chain fatty acids within the preterm gastrointestinal tract immediately after birth might predispose neonates to exacerbated gut inflammation. Some of the findings, including the elevated fecal mevalonate levels, are potential biomarkers in neonatology for early identification of metabolic disturbances linked to gut inflammation, emphasizing further studies to explore its association with inflammatory conditions in preterm infants. Inflammatory markers that can predict intestinal disorders are insufficiently characterized in preterm neonates. This study identified antimicrobial peptide responses, proteolytic activity, marked dysbiosis, and reduced short-chain fatty acid production in feces from preterm neonates. These critical differences in inflammatory, metabolomic, and microbial signatures may predispose to exacerbated gut inflammation in preterm neonates. Some inflammatory effectors in feces are potential biomarkers for the early detection of intestinal inflammatory conditions in preterm neonates. This study contributes to understanding the inflammatory conditions in the guts of preterm babies and identifies novel targets for timely diagnosis, interventions, and management practices in neonatal care.

Increased fecal glycocholic acid levels correlate with obesity in conjunction with the depletion of archaea: the DOSANCO Health Study.

Recent studies have focused on the relationship between obesity and gut microbiota. This study aims to identify fecal components and gut bacterial species associated with different BMI categories. In this study, 538 participants aged ≥18 years were categorized into underweight, normal, and obese groups based on BMI (cutoffs: 18.5 and 25.0 kg/m²). We compared 30 fecal components among these groups and calculated correlation coefficients between each component and BMI. Participants were then divided into quartiles based on fecal component levels correlated with BMI, and the prevalence ratio (PR) of obesity was calculated, adjusted for confounding factors. We also analyzed the composition and diversity of gut microbiota and bacterial gene expression among the quartiles for each fecal component. Fecal glycocholic acid (GCA) showed a significant positive correlation with BMI. The PR for obesity in the highest quartile of fecal GCA was 3.30 (95% CI: 1.21-9.54), indicating a significantly higher risk of obesity compared to the lowest quartile. Gut microbiota analysis revealed significant differences in the abundance of Ruminococcaceae Incertae Sedis, Faecalibacterium, and Methanobrevibacter, with Methanobrevibacter being absent in the higher quartiles of fecal GCA. Additionally, gene expression for enzymes involved in the deconjugation of conjugated bile acids, including GCA, was downregulated in the highest quartile. Increased fecal GCA levels are positively correlated with obesity, alongside a depletion of archaea.

Dietary supplementation with Epimedium contributes to the improvement of hormone levels, gut microbiota, and serum metabolite composition in the Chinese forest musk deer (Moschus berezovskii)

The Chinese forest musk deer (Moschus berezovskii) is a small ruminant animal with special economic value. It is listed as a National Level I key protected species in China. However, these animals are prone to stress responses in captive environments. Epimedium, a traditional Chinese herb with aphrodisiac and anti-stress properties, may have potential benefits for the health of the captive Chinese forest musk deer, though its efficacy requires further investigation. This study aimed to evaluate the effects of dietary supplementation with Epimedium on the hormone levels, gut microbiota composition, and serum metabolism of the Chinese forest musk deer. The fourteen adult male Chinese forest musk deer with similar initial body weights (7.0 ± 0.3 kg) and an average age of 4.5 years were randomly divided into two groups, each containing seven animals. The control group was fed a standard diet without Epimedium, while the Epimedium group received the standard diet supplemented with 15 g Epimedium /kg DM. The results indicated that the inclusion of Epimedium in the diet increased dry matter intake (DMI) and improved the ratio of feed to gain (F/G), with an increase in fecal testosterone levels (p &amp;lt; 0.05). 16S rDNA sequencing analysis revealed that Epimedium enhanced the richness and diversity of the gut microbiota in the Chinese forest musk deer, increasing the relative abundance of beneficial bacteria such as Firmicutes, while reducing the relative abundance of the potentially pathogenic Proteobacteria (p &amp;lt; 0.05). A widely targeted metabolomics analysis identified 25 differential metabolites between the two groups. Significant alterations were observed in key metabolic pathways related to lipid metabolism, hormone regulation, and antioxidation, such as ovarian steroidogenesis, tyrosine metabolism, and glycerophospholipid metabolism. Furthermore, correlation analysis between gut microbiota and serum differential metabolites showed that the relative abundances of Clostridia_vadinBB60_group and UCG-010 were positively correlated with anserine and 7-ketocholesterol, respectively (p &amp;lt; 0.05). In conclusion, Epimedium positively influenced feed intake and hormone levels in the Chinese forest musk deer by modulating gut microbiota composition and serum metabolism.

DOP091 Early serum infliximab levels predict outcomes in Acute Severe Ulcerative Colitis: results from PREDICT-UC

Abstract Background The utility of infliximab (IFX) therapeutic drug monitoring (TDM) in acute severe ulcerative colitis (ASUC) is unclear. We aimed to assess whether IFX levels are associated with outcomes in ASUC. Methods PREDICT-UC (NCT02770040) was a randomised controlled trial that compared dosing strategies in 138 steroid-refractory ASUC patients.1 Serum and faecal IFX levels were quantified by ELISA (MabTrack level infliximab, Essange Reagents, Netherlands) after conclusion of the trial and correlated with outcomes: IFX response by day 7 (Lichtiger score [LS]&amp;lt;10, with ≥3-point reduction and decrease in rectal bleeding and stool frequency ≤4/day); eventual response by day 14 (LS&amp;lt;10); and colectomy by month 3. Individual IFX clearance was estimated using a two-compartment pharmacokinetic model with fixed V1, V2 and Q. Results 681 serum IFX levels were available across 135 patients; 91 received an initial 5mg/kg and 44 an initial 10mg/kg IFX dose. 85 responded by day 7 and 17 required colectomy by month 3. Post-IFX serum levels were higher on days 1 and 3 (median ug/mL, IQR) in the 10mg/kg group (175.4, 137.2-202.7 and 116.3, 83.4-132.9) compared to the 5mg/kg group (91.8, 77.2-109.4 and 56.0, 46.0-67.0; each P&amp;lt;0.001). Day 1 and day 3 serum IFX levels were not significantly different in responders and non-responders. A higher day 3:day 1 serum IFX ratio predicted response (63.1%, IQR 56.0-72.1 vs 58.1%, IQR 51.6-62.8, P=0.006; AUC 0.67). A lower day 3 serum IFX level predicted colectomy (51.0, IQR 39.2-57.4 vs 69.0, IQR 51.1-101.7, P=0.003; AUC 0.23). IFX clearance using serum levels between days 1-7 was higher in non-responders compared to responders (0.72L/day, IQR 0.55-0.89 vs 0.56L/day, IQR 0.39-0.72, P&amp;lt;0.001) and in patients who had colectomy (P=0.011). Patients with high clearance (≥0.62L/day) were more likely to respond to an initial 10mg/kg vs 5mg/kg IFX dose (RR 1.50, 95%CI 1.01-2.23, P=0.046), and more likely to require colectomy if they received an initial 5mg/kg vs 10mg/kg dose (HR 4.81, 95%CI 1.09-21.37, P=0.039). In patients with high clearance who did not respond initially, response by day 14 was higher in those receiving a second 10mg/kg dose compared to 5mg/kg (10/26 [38%] vs 1/9 [11%]; RR 3.43, 95%CI 1.05-11.19, P=0.041). Day 1 and 3 faecal IFX correlated with IFX clearance (both rho=0.36, both P&amp;lt;0.001), CRP and the UCEIS (including bleeding and erosion/ulcer sub-scores). Conclusion Elevated day 3:day 1 serum IFX ratio was associated with IFX response by day 7. Early IFX clearance predicted IFX response and month 3 colectomy. High IFX clearance may be overcome by higher IFX dosing, resulting in improved response and reduced colectomy rates. Early IFX level quantification can help predict outcomes in ASUC.

P0509 Fecal calprotectin diagnostic level gradient along the small bowel in patients with Crohn’s disease

Abstract Background Fecal calprotectin (FC) is known to be a sensitive biomarker of colonic inflammation but to a lesser degree of small bowel (SB) inflammation. Moreover, data on FC’s diagnostic levels in different SB segments are scarce. We aimed to examine FC’s diagnostic levels along the SB-axis in CD. Methods This was a post-hoc aggregated analysis of five prospective studies of adult CD patients, who underwent FC testing and SB video capsule endoscopy (VCE). Lewis score (LS) inflammation in different SB segments was tested for correlation with FC level after exclusion of colonic disease. The diagnostic levels of FC for SB inflammatory topographical-gradient were assessed using a receiver operating characteristic. Results 214 patients were included (age:30 [24-43] year-old, males-57%). For a similar SB inflammatory-activity (LS≥135), FC levels incrementally increased from proximal to distal SB segments (63 [30-121] versus 190 [78-549], p=0.005) and from distal SB segment to the colon (190 [78-549] versus 542 [185-1000], p=0.010). The best FC cutoffs to identify isolated mild proximal/distal SB-inflammation (LS≥135) were 77 and 123, respectively. A cutoff of 234 was best to detect more significant proximal inflammation (LS≥350) when only mild distal SB-inflammation was present. In sensitivity analyses, this proximal-to-distal FC gradient was maintained when LS≥350 and LS≥790 were used as the inflammatory reference-values. Unlike FC, the magnitude of CRP elevation was unrelated to the topography of inflammation along the SB-axis. Conclusion FC may serve as a topographical biomarker of CD-activity, with its sensitivity to identify mucosal inflammation increases from proximal to distal SB segments.

P0205 Fecal host transcriptomics accurately assesses endoscopic inflammatory activity in patients with inflammatory bowel diseases

Abstract Background The intestinal mucosa regenerates every few days, and cells are continuously shed into the gut lumen. These cells, primarily epithelial and immune cells, have recently been shown to remain viable after shedding and hold critical information for assessing bowel pathology. Analysis of endoscopic washes of luminal material during colonoscopies suggests that the human transcriptome in fecal material accurately reflects degree of histologic inflammation in patients with inflammatory bowel diseases (IBD). We aimed to define whether transcriptomic analysis of stool samples can reflect degree of intestinal inflammation in patients with IBD. Methods Bulk RNA sequencing was performed on stool samples to obtain fecal human transcriptomes from 82 IBD patients, as well as from healthy controls. Each sample received an inflammation score derived from a group of pro-inflammatory transcripts. Inflammatory score was compared to fecal calprotectin as well as endoscopic evaluation. Results The quality of human RNA isolated from fecal content was high, with a median of 2,218 human genes detected per sample. The correlation between fecal calprotectin protein levels and mRNA expression was high (r=0.75). An inflammatory score was generated based on a group of differentially expressed genes. The inflammatory score provided high sensitivity and specificity (both 90%) in predicting endoscopic inflammatory activity when compared to colonoscopic findings. Conclusion Fecal shed cell transcriptomics provided a novel non-invasive tool to measure inflammatory activity at the endoscopic level in patients with IBD. Ongoing studies will address whether this technology can assist in defining degree and location of inflammation, as well as predict response to different therapies.

DOP057 Early serum and faecal cytokines predict clinical outcomes in Acute Severe Ulcerative Colitis: results from PREDICT-UC

Abstract Background Acute severe ulcerative colitis (ASUC) is a medical emergency with variable outcomes. We aimed to evaluate whether early serum and faecal cytokine levels predict treatment response. Methods Serum and stool were collected from patients with ASUC. Steroid-refractory patients received infliximab (IFX, monoclonal antibody to tumour necrosis factor [TNF]) as part of PREDICT-UC (NCT02770040), a multi-centre randomised controlled trial that evaluated escalated infliximab (IFX) dosing.1 Specimens were collected at screening, and if steroid-refractory at days 1 and 3 post-IFX. Response to first IFX dose was assessed by day 7. Interleukin (IL)-6 and TNF levels were quantified using ELISA after clinical study conclusion. Results Within the cohort of 190 patients, 54 were steroid-responsive and 136 steroid-refractory and received IFX. Of the steroid-refractory patients, 85 (62.5%) were IFX responders and 51 (37.5%) were IFX non-responders. 17/136 (12.5%) patients underwent colectomy by 3 months. Steroid response At screening, serum IL-6 was higher in steroid non-responders compared to responders (10.5 pg/mL vs 3.5 pg/mL, P&amp;lt;0.001), whereas faecal IL-6 was similar in both groups (154.7 pg/mL vs 138 pg/mL, P=0.09). Faecal TNF at screening was higher in non-responders compared to responders (48.6 pg/mL vs 14.6 pg/mL, P=0.032). IFX response Serum IL-6 at was higher in IFX non-responders compared to responders at all timepoints (P&amp;lt;0.005); however, this finding was not observed with faecal IL-6. Whilst faecal TNF at screening, days 0 and 1 did not differ between IFX responders and non-responders, median day 3 faecal TNF was suppressed below detection limits (&amp;lt;1.56 pg/mL) in IFX responders compared to 4.4 pg/mL in non-responders (P=0.006, AUC=0.65). Colectomy by month 3 Higher serum IL-6 at screening (P=0.009, AUC=0.71) and day 1 (P=0.002, AUC=0.75) were associated with month 3 colectomy. Similarly, day 3 faecal IL-6 was higher in patients who required colectomy versus those who did not (159.0 pg/mL vs 110.7 pg/mL, P=0.02, AUC 0.69). Median faecal TNF at day 3 post-IFX was 6.3 pg/mL in patients who required colectomy but dropped below detection limit in those who avoided colectomy (P=0.004). Day 3 faecal TNF predicted colectomy (AUC=0.72) with a threshold of ≥7.07 pg/mL on Youden’s index having 50% sensitivity, 89.8% specificity, 43.8% PPV and 91.9% NPV. Conclusion Early serum and faecal cytokines predict outcomes in ASUC. Faecal TNF persistence 3 days after IFX is associated with non-response and colectomy, and might help identify patients who benefit from early IFX re-dosing. IL-6 elevation in non-responders suggests activation of an alternate immune pathway that may benefit from non-TNF-targeted therapy.

DOP028 The resolution of fecal calprotectin configurations and their biological functions in gut inflammation

Abstract Background Fecal calprotectin (CP) serves as a worldwide established biomarker used for the diagnosis and management of inflammatory bowel diseases (IBD). However, the biological function of CP in the human gut is still unknown and numerous studies obtained contradictory results. Calprotectin is mainly described to be present as a tetrameric protein complex (S100A8/S100A9)2, while the quaternary protein structure (configuration) of S100A8 and S100A9 in the human gut lumen remains enigmatic.1 In this study we resolved the fecal protein configurations of calprotectin and their biological functions in IBDs. Methods We defined biological functions of S100A8 and S100A9 dimers by antibody-mediated immunoprecipitation of S100A8 and S100A9 from stool obtained from IBD patients coupled with subsequent LC-MS/MS analysis. Next, we analysed human colonic organoids by single-cell RNA sequencing after S100A8 or S100A9 stimulation. Moreover, we orally exposed mice to recombinant human S100A8 and S100A9 protein during experimental gut inflammation and genetically inactivated S100a9 in toxic and genetic mouse models. To identify the protein configurations of S100A8 and S100A9 in the human gut lumen we examined stool samples from IBD patients using size-exclusion chromatography and LC-MS/MS analysis. Results We demonstrate pro-inflammatory actions for S100A8 and S100A9 dimers as oral administration of human S100A8 and S100A9 homodimers, but not CP, worsened experimental enteritis and colitis. In accordance, multi-omic phenotyping revealed that human S100A8 and S100A9 homodimers induce the NLRP1 inflammasome in intestinal epithelium. In turn, genetic deletion of S100a9 ameliorated experimental gut inflammation. S100A8 and S100A9 dimers were frequently detectable in stool from IBD patients from three independent IBD cohorts, but not in healthy individuals. More specifically, fecal S100A9 detection was associated with clinical and endoscopic disease activity in IBD patients with low fecal CP levels (≤150µg/g). Importantly, four fecal CP assays in clinical use were not able to detect S100A8 and S100A9 homodimers. Conclusion Our study is the first to reveal the presence of S100A8 and S100A9 dimers in stool from IBD patients. Moreover, we demonstrate a diagnostic gap for fecal CP assays in clinical use. We establish that fecal S100A9 detection is associated with endoscopic disease activity in IBD patients in which fecal CP fails to identify active disease. We reveal disease-modifying functions for S100A8 and S100A9 homodimers by inducing the NLRP1 inflammasome, while the same effects were not observable for calprotectin. Taken together, our findings may reflect a major advance in the IBD biomarker field. References Jukic, A., Bakiri, L., Wagner, E. F., Tilg, H. &amp; Adolph, T. E. Calprotectin: from biomarker to biological function. Gut 70 , 1978-1988 (2021). https://doi.org/10.1136/gutjnl-2021-324855

P1342 Characteristics of the gut microbiota of patients with concomitant inflammatory bowel disease and psoriatic arthritis

Abstract Background Inflammatory bowel disease (IBD) and psoriatic arthritis (PsA) are immune-mediated diseases (IMDs) that have been independently related to shifts in the gut microbiota. In this pilot study, we analyzed whether, in patients in whom both IMIDs coexist, the composition and function of the gut microbiota is different from when only one of the two IMDs exists. Methods Transversal observational study performed at a Spanish tertiary hospital. Ten patients with concomitant IBD and PsA (group A) were included. Two age, gender and disease duration matched control groups were also created, one with IBD-only patients (group B, n=20), and another with PsA-only patients (group C, n=20). Demographic and clinical characteristics were recorded. Stool samples were collected and the variable region V3–V4 of the bacterial 16S rRNA genes present in the feces was PCR-amplified and the resulting amplicons were sequenced on an Illumina NovaSeq 6000 instrument. Short chain fatty acids (SCFA) were analyzed by gas chromatography from the supernatants of the homogenized feces. Dietary assessment was registered by an online food frequency questionnaire specifically designed for intestinal disturbances; foods were transformed into nutrients and dietary compounds. For statistical analysis, ANOVA was used to compare the three groups (when the ANOVA was significant [p&amp;lt;0.05], Bonferroni's test was used for post-hoc comparisons). Results Globally, the microbiota of the different study groups did not show major rearrangements, with alpha diversity not showing statistically significant differences between them. However, beta diversity analyses indicated that the microbiotas of groups C and B were statistically different, with group A occupying an intermediate position. A linear discriminant analysis of the effect size showed that group A was enriched in certain microorganisms such as Akkermansia, while group C was enriched in Bacteroides (Figure 1). The quantification of the fecal levels of SCFA showed no statistical significant differences between the three groups. Moreover, no significant differences were observed regarding energy and nutrient intake between the assessed groups. Conclusion Our results suggest the existence of different gut microbiota profiles in subjects suffering from PsA or IDB, while patients with both conditions have an intermediate composition. These differences do not see to result from different dietary habits, since no differences in nutrient or energy intake between the groups were observed.

Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer’s disease pathologic process via GPR41 and GPR43

BackgroundAlzheimer’s disease (AD) is a prevalent neurodegenerative disease (ND). In recent years, multiple clinical and animal studies have shown that mitochondrial dysfunction may be involved in the pathogenesis of AD. In addition, short-chain fatty acids (SCFA) produced by intestinal microbiota metabolism have been considered to be important factors affecting central nervous system (CNS) homeostasis. Among the main mediators of host-microbe interactions, volatile fatty acids play a crucial role. Nevertheless, the influence and pathways of microorganisms and their metabolites on Alzheimer’s disease (AD) remain uncertain.ResultsIn this study, we present distinctions in blood and fecal SCFA levels and microbiota composition between healthy individuals and those diagnosed with AD. We found that AD patients showed a decrease in the abundance of Akkermansia muciniphila and a decrease in propionic acid both in fecal and in blood. In order to further reveal the effects and the mechanisms of propionic acid on AD prevention, we systematically explored the effects of propionic acid administration on AD model mice and cultured hippocampal neuronal cells. Results showed that oral propionate supplementation ameliorated cognitive impairment in AD mice. Propionate downregulated mitochondrial fission protein (DRP1) via G-protein coupled receptor 41 (GPR41) and enhanced PINK1/PARKIN-mediated mitophagy via G-protein coupled receptor 43 (GPR43) in AD pathophysiology which contribute to maintaining mitochondrial homeostasis both in vivo and in vitro. Administered A. muciniphila to AD mice before disease onset showed improved cognition, mitochondrial division and mitophagy in AD mice.ConclusionsTaken together, our results demonstrate that A. muciniphila and its metabolite propionate protect against AD-like pathological events in AD mouse models by targeting mitochondrial homeostasis, making them promising therapeutic candidates for the prevention and treatment of AD.2Eefw-diaDYPDEcqvaR2iqVideo

Body composition changes and clinical outcomes in pediatric cystic fibrosis during 24 months of lumacaftor ivacaftor therapy based on real-world data

Clinical trials demonstrate the short-term efficacy of dual CFTR modulators, but long-term real-world data is limited. We aimed to investigate the effects of 24-month lumacaftor/ivacaftor (LUM/IVA) therapy in pediatric CF patients (pwCF). This observational study included pwCF homozygous for F508del mutation treated between 2021 and 2023. We report data for the first 24 months from therapy initiation. Variables were analyzed separately for ages 2–5, 6–11, and over 12. Data from 49 pwCF (median age: 9.3 years (5.5–14.2)) showed that ppFEV1 values after a transient increase at 12 months, decreased from 102% (82–114) at baseline to 87% (74–96) at 24 months. The decrease was more pronounced with higher initial ppFEV1. Median sweat chloride concentration decreased from 75 mmol/L (69–82) to 57 mmol/L (43–70) without any association with respiratory function change. Median BMI z-score increased from − 0.81 (− 1.37–0.49) to − 0.39 (− 0.88 to − 0.04) (p = 0.288), and the proportion of underweight and overweight children decreased. Skeletal muscle mass remained stable, while fat mass significantly increased (p = 0.011). Fecal elastase levels improved, especially among younger patients. These findings underscore the potential benefits of early initiation of CFTR modulator therapy in pediatric CF patients, highlighting improvements in nutritional status and pancreatic function.

High leafy and root vegetables and high rice dietary patterns were associated with primary and secondary bile acid levels in the feces

Colorectal cancer has the second highest mortality among cancer sites worldwide, with increasing morbidity, high recurrence rates, and even poorer postoperative quality of life. Therefore, preventive strategies for colorectal cancer should be established. This study aimed to cross-sectionally explore dietary patterns affecting the intestinal metabolism of bile acids (BAs), a risk factor for colorectal cancer, in young Japanese women. We collected fecal samples for intestinal microbiota and BA analysis. We used the Bristol scale to determine 1-week defecation status. Moreover, the brief-type self-administered diet history questionnaire was used for habitual dietary intake status. Reduced-rank regression analysis revealed dietary patterns related to fecal BA levels. The relationship between dietary patterns and fecal BA levels was adjusted for defecation status and intestinal microbiota variables using analysis of covariance. Reduced-rank regression analysis generated two dietary pattern scores related to fecal BA levels. First, the score was associated with a greater intake of leafy and root vegetables, and higher values were associated with greater fecal cholic and chenodeoxycholic acid levels and lower deoxycholic and lithocholic acid levels. Second, the score was associated with greater rice intake and lower Western sweets, pork, beef, and egg intake, and higher values were associated with lower deoxycholic and lithocholic acid levels. These relationships remained after adjusting for intestinal microbiota and defecation status variables.

Fecal propionate is a signature of insulin resistance in polycystic ovary syndrome.

To investigate the roles of fecal short-chain fatty acids (SCFAs) in polycystic ovary syndrome (PCOS). The levels of SCFAs (acetate, propionate, and butyrate) in 83 patients with PCOS and 63 controls were measured, and their relationships with various metabolic parameters were analyzed. Intestinal microbiome analysis was conducted to identify relevant bacteria. The study took place at the Center for Reproductive Medicine at Shengjing Hospital of China Medical University in Shenyang, from 5 February to 23 May 2023. Logistic regression analyses were used to investigate the relationships between SCFAs, PCOS, and PCOS-related insulin resistance (IR). Differences in bacterial populations between women with PCOS-IR and those with PCOS-non-insulin resistance (NIR) were identified using linear discriminant analysis effect Size (LEfSe). The relationships between bacteria and fecal propionate levels were explored through linear regression analyses. The potential of fecal propionate and microbial profiles as biomarkers for insulin resistance in PCOS patients was assessed using receiver operating characteristic (ROC) curve analysis. Higher fecal propionate levels were observed in patients with PCOS compared to controls (p = 0.042) and in PCOS-IR compared to PCOS-NIR (p = 0.009). There was no significant difference in fecal propionate levels between the IR and NIR subgroups of women in the control group (p > 0.05). Additionally, higher fecal propionate levels were associated with IR in PCOS (p = 0.039; OR, 1.115; 95% CI, 1.006-1.237). The abundance of Prevotella copri and Megamonas funiformis was higher in PCOS-IR women compared to PCOS-NIR women (LDA score > 3) and correlated with fecal propionate levels (adjusted R² = 0.145, p < 0.001). The area under the curve (AUC) for propionate and the combined presence of P. copri and M. funiformis in predicting PCOS was 78.0%, with a sensitivity of 78.5% and a specificity of 72.4%. Pathways related to carbohydrate metabolism were significantly enriched in the microbiota of the PCOS-IR population but not in the control IR group. Higher fecal propionate levels correlate with PCOS-related insulin resistance. P. copri and M. funiformis might be key functional bacteria. Therefore, the combination of propionate levels and the abundance of these two bacteria may serve as a potential biomarker for insulin resistance in PCOS patients. Regulation of the intestinal microbiome might be beneficial for the metabolic health of women with PCOS.

Effect of Relocation, Social Housing Changes, and Diarrhea Status on Microbiome Composition of Juvenile Cynomolgus Macaques (Macaca fascicularis).

Social housing changes are likely stressful and can be associated with diarrhea, the most common health problem noted in captive macaque populations. Diarrhea may reflect a negative shift in the gut flora ("gut dysbiosis"). This study reported on changes in the gut microbiome composition of juvenile primates (Macaca fascicularis) that experienced a change in social housing and exhibited diarrhea. A matched-case-control design was utilized to compare fecal samples from gut-unhealthy animals to healthy counterparts (n = 61). Baseline samples from recently imported animals were collected during routine sedation events. When an animal experienced a housing change, the entire cohort was monitored for diarrhea. Post-relocation samples were collected from animals that exhibited diarrhea and from their matched controls. Samples were assessed via 16S rRNA next-generation sequencing for a microbiome analysis and by ELISA for cortisol levels. Fecal cortisol levels did not differ between groups or across time points. Alpha diversity increased after relocation and differed by sex with males demonstrating a greater change in alpha diversity (p < 0.01). Although exhibiting diarrhea did not affect alpha diversity levels, it was associated with increased beta diversity (p < 0.05). Understanding how the microbiome may be affected by relocation will help guide prevention strategies such as the use of specific probiotics to reduce the incidence of diarrhea.

Variation in faecal testosterone levels in male gray whales on a foraging ground relative to maturity and timing.

Understanding wildlife reproductive seasonality is crucial for effective management and long-term monitoring of species. This study investigates the seasonal variability of testosterone in male Pacific Coast Feeding Group (PCFG) gray whales, using an eight-year dataset (2016-2023) of individual sightings, drone-based photogrammetry and endocrine analysis of faecal samples. We analyzed the relationship between faecal testosterone levels and total body length (TL), body condition (body area index, BAI), sexual maturity and day of the year using generalized additive mixed models. Our findings reveal a significant increase in faecal testosterone levels in mature males (MM) towards the end of the foraging season. This increase was not observed in JM, highlighting age-dependent development of sexual characteristics. No significant relationship was found between testosterone levels and TL. Additionally, BAI was not significantly associated with testosterone levels. Our results suggest that the increasing testosterone levels in MM gray whales may indicate preparation for mating before the southbound migration. These findings provide valuable insights into the reproductive biology of PCFG gray whales and underscore the importance of non-invasive faecal sampling for studying reproductive seasonality in large whales. Our approach not only provides further insights into the seasonality of male reproduction for the PCFG gray whales but also offers tools to enhance the understanding of male reproduction in baleen whales broadly with non-invasive approaches.

Contaminant-degrading bacteria are super carriers of antibiotic resistance genes in municipal landfills: A metagenomics-based study.

Municipal landfills are hotspot sources of antimicrobial resistance (AMR) and are also important habitats of contaminant-degrading bacteria. However, high diversity of antibiotic resistance genes (ARGs) in landfills hinders assessing AMR risks in the affected environment. More concerned, whether there is co-selection or enrichment of antibiotic-resistant bacteria and contaminant-degrading bacteria in these extremely polluted environments is far less understood. Here, we collected metagenomic datasets of 32 raw leachate and 45 solid waste samples in 22 municipal landfills of China. The antibiotic resistome, antibiotic-resistant bacteria and contaminant-degrading bacteria were explored, and were then compared with other environmental types. Results showed that the antibiotic resistome in landfills contained 1,403 ARG subtypes, with the total abundance over the levels in natural environments and reaching the levels in human feces and sewage. Therein, 49 subtypes were listed as top priority ARGs for future surveillance based on the criteria of enrichment in landfills, mobilizable and present in pathogens. By comparing to those in less contaminated river environments, we elucidated an enrichment of antibiotic-resistant bacteria with contaminant-degrading potentials in landfills. Bacteria in Pseudomonadaceae, Moraxellaceae, Xanthomonadaceae and Enterobacteriaceae deserved the most concerns since 72.2% of ARG hosts were classified to them. Klebsiella pneumoniae, Acinetobacter nosocomialis and Escherichia coli were abundant multidrug-resistant pathogenic species in raw leachate (∼10.2% of total microbiomes), but they rarely carried contaminant-degradation genes. Notably, several bacterial genera belonging to Pseudomonadaceae had the most antibiotic-resistant, pathogenic, and contaminant-degrading potentials than other bacteria. Overall, the findings highlight environmental selection for contaminant-degrading antibiotic-resistant pathogens, and provide significant insights into AMR risks in municipal landfills.

Tartary Buckwheat Bran and Fructus Aurantii Combination (TBB-FA): A Promising Therapeutic Approach for Functional Dyspepsia via Modulation of Gut Microbiota, Short-Chain Fatty Acids and Purine Signaling Pathway.

This study evaluates the therapeutic impact of Fructus aurantii (FA) stir-baked with tartary buckwheat bran (TBB) on functional dyspepsia (FD), employing a reserpine at the dose of 5 mg/kg to rats. FA, a traditional Chinese herbal medicine, is processed with TBB to enhance its gastrointestinal motility benefits. The study's objectives were to assess the impact of this preparation on intestinal flora, SCFA levels, and metabolomic profiles in FD. Rats were divided into groups receiving different treatments, with the TBB-FA group showing a 7.15-33.2 times increase in fecal SCFA levels, specifically propionate and butyrate, compared to the Fructus aurantii (FA) stir-baked with wheat bran (WB) group (WB-FA) (p < 0.05). Metabolomics identified 23 serum and 11 intestinal mucosal biomarkers associated with FD, predominantly linked to the purine metabolic pathway. Results indicated a significant positive correlation (r ≥ 0.7) between the abundance of Bacteroides and the expression of propionate and isobutyrate in fecal samples post-TBB-FA treatment. This suggests that TBB-FA may enhance beneficial gut bacteria and SCFA production, potentially modulating the purinergic signaling pathway, which is implicated in gastrointestinal motility. In conclusion, the study demonstrates that TBB-FA could be a promising therapeutic approach for FD by improving gut microbiota and SCFA levels and highlights the purinergic signaling pathway as a novel target for treatment. The findings pave the way for further research into the integration of traditional Chinese medicine and modern therapeutic strategies for FD.

Early-life enrichment in American mink (Neogale vison): Enrichment of the perinatal environment improves maternal nest building and reduces stereotypic behaviour

Abstract Pens for farmed mink (Neogale vison) commonly include separate nesting areas to provide privacy and warmth in the perinatal period. However, standard bedding materials may not be sufficient to allow intrinsically motivated nest-building behaviours in dams. Further, these materials may not produce optimal nest structures for the rearing of kits. In the present study, we provided extra, relatively high-quality nest-building materials and a chewable sisal rope enrichment for mink dams in the perinatal period (a group enriched at whelping; EW). The effects of these enrichments on various measures of welfare and maternal behaviour were compared to those of mink dams in standard housing (SH) and mink dams whose kits were enriched later in development (EK). EW dams performed less stereotypic behaviour and built higher quality nests than dams of other housing conditions, although dams’ basal faecal cortisol metabolite levels (FCM) were not affected. The stress responsiveness of these dams’ offspring was later assessed by sampling FCM before and after a handling event, however, this event did not appear to induce a measurable stress response and thus no conclusions could be drawn regarding effects of perinatal enrichment on HPA-axis development. Overall, provision of higher quality nest-building materials and a chewable rope enrichment benefited dam stereotypic behaviour and nest building in the perinatal period. We present suggestions for future studies to further investigate whether perinatal enrichment can impact maternal care and offspring HPA-axis development in mink.