Fecal Markers Research Articles

Underdevelopment of the gut microbiota and bacteria species as non-invasive markers of prediction in children with autism spectrum disorder

ObjectiveThe gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota...

Microbial Find, Inform, and Test Model for Identifying Spatially Distributed Contamination Sources: Framework Foundation and Demonstration of Ruminant Bacteroides Abundance in River Sediments.

Microbial pollution in rivers poses known ecological and health risks, yet causal and mechanistic linkages to sources remain difficult to establish. Host-associated microbial source tracking (MST) markers help to assess the microbial risks by linking hosts to contamination but do not identify the source locations. Land-use regression (LUR) models have been used to screen the source locations using spatial predictors but could be improved by characterizing transport (i.e., hauling, decay overland, and downstream). We introduce the microbial Find, Inform, and Test (FIT) framework, which expands previous LUR approaches and develops novel spatial predictor models to characterize the transported contributions. We applied FIT to characterize the sources of BoBac, a ruminant Bacteroides MST marker, quantified in riverbed sediment samples from Kewaunee County, Wisconsin. A 1 standard deviation increase in contributions from land-applied manure hauled from animal feeding operations (AFOs) was associated with a 77% (p-value <0.05) increase in the relative abundance of ruminant Bacteroides (BoBac-copies-per-16S-rRNA-copies) in the sediment. This is the first work finding an association between the upstream land-applied manure and the offsite bovine-associated fecal markers. These findings have implications for the sediment as a reservoir for microbial pollution associated with AFOs (e.g., pathogens and antibiotic-resistant bacteria). This framework and application advance statistical analysis in MST and water quality modeling more broadly.

Evaluation of Sampling, Analysis, and Normalization Methods for SARS-CoV-2 Concentrations in Wastewater to Assess COVID-19 Burdens in Wisconsin Communities

Wastewater surveillance for SARS-CoV-2 provides an approach for assessing the infection burden across a sewer service area. For these data to be useful for public health, measurement variability and the relationship to case data need to be established. We determined SARS-CoV-2 RNA concentrations in the influent of 12 wastewater treatment plants from August 2020 to January 2021. Technical replicates for N1 gene concentrations showed a relative standard deviation of 24%, suggesting it is possible to track relatively small (∼30%) changes in SARS-CoV-2 concentrations over time. COVID-19 cases were correlated significantly (ρ ≥ 0.70) to wastewater SARS-CoV-2 RNA concentrations across large and small service areas, with weaker relationships (ρ ≥ 0.59) in two communities. SARS-CoV-2 concentrations normalized to per capita slightly improved correlations to COVID-19 incidence, but normalizing to a spiked recovery control (BCoV) or a fecal marker (PMMoV or HF183) reduced correlations for a number of plants. Daily sampling demonstrated that a minimum of two samples collected per week were needed to maintain accuracy in trend analysis. The differences in the strength of SARS-CoV-2 relationships to COVID-19 incidence and the effect of normalization on these data among communities demonstrate that rigorous validation should be performed at individual sites where wastewater surveillance programs are implemented.

Bather Shedding as a Source of Human Fecal Markers to a Recreational Beach.

Microbial source tracking (MST) can identify and locate surf zone fecal indicator bacteria (FIB) sources. However, DNA-based fecal marker results may raise new questions, since FIB and DNA marker sources can differ. Here, during 2 years of summertime (dry season) MST for a Goleta, California recreational beach, surf zone FIB were mainly from gulls, yet low level human-associated DNA-based fecal marker (HF183) was detected in 25 and 14% of surf zone water samples, respectively. Watershed sources were hypothesized because dry weather creek waters had elevated FIB, and runoff-generating rain events mobilized human (and dog) fecal markers and Salmonella spp. into creeks, with human marker HF183 detected in 40 and 50% of creek water samples, dog markers detected in 70 and 50% of samples, and Salmonella spp. in 40 and 33.3% of samples, respectively over 2 years. However, the dry weather estuary outlet was bermed in the first study year; simultaneously, creek fecal markers and pathogens were lower or similar to surf zone results. Although the berm breached in the second year, surf zone fecal markers stayed low. Watershed sediments, intertidal beach sands, and nearshore sediments were devoid of HF183 and dog-associated DNA markers. Based on dye tests and groundwater sampling, beach sanitary sewers were not leaking; groundwater was also devoid of HF183. Offshore sources appeared unlikely, since FIB and fecal markers decreased along a spatial gradient from the surf zone toward nearshore and offshore ocean waters. Further, like other regional beaches, surf zone HF183 corresponded significantly to bather counts, especially in the afternoons when there were more swimmers. However, morning detections of surf zone HF183 when there were few swimmers raised the possibility that the wastewater treatment plant (WWTP) offshore outfall discharged HF183 overnight which transported to the surf zone. These findings support that there may be lowest achievable limits of surf zone HF183 owing to several chronic and permanent, perhaps diurnal, low concentration sources.

Sources of Low Level Human Fecal Markers in Recreational Waters of Two Santa Barbara, CA Beaches: Roles of WWTP Outfalls and Swimmers

Worldwide, fecal indicator bacteria (FIB) evidence coastal water contamination for which sources are unknown. Here, for two FIB-impacted Santa Barbara recreational beaches, hypothesized fecal sources were investigated over three dry seasons (summers) using nearly 2000 field samples of water (ocean, creek, groundwater), sand, sediments, effluent and fecal sources. In years 1 and 2, gull and dog feces were identified as the probable main FIB sources to surf zone waters, yet HF183 human fecal markers were consistently detected. Determining HF183 sources was therefore prioritized, via year 3 sub-studies. In lower watersheds, human and dog wastes were mobilized by small storms into creeks, but no storm drain outfalls or creeks discharged into surf zones. Beach area bathrooms, sewers, and a septic system were not sources: dye tracing discounted hydraulic connections, and shallow groundwater was uncontaminated. Sediments from coastal creeks and downstream scour ponds, nearshore marine sediments, and sands from inter- and supratidal zones contained neither HF183 nor pathogens. Two nearby wastewater treatment plant (WWTP) outfalls discharged HF183 into plumes that were either deep or distant with uncertain onshore transport. Regardless, local sources were evidenced, as surf zone HF183 detection rates mostly exceeded those offshore and nearshore (around boat anchorages). The presence of swimmers was associated with surf zone HF183, as swimmer counts (on weekdays, holidays, weekends, and during races) significantly correlated (p<0.05, n = 196) to HF183 detections. Besides comprehensively assessing all possible fecal sources, this study provides new explanations of chronic low-level human markers in recreational beach surf zones, suggesting likely lowest achievable HF183 thresholds.

Serum and Fecal Markers of Intestinal Inflammation and Intestinal Barrier Permeability Are Elevated in Parkinson's Disease.

Parkinson’s disease (PD) is characterized by alpha-synuclein misfolding with subsequent intraneuronal amyloid formation and accumulation, low grade neuroinflammatory changes, and selective neurodegeneration. Available evidence suggests that the pathology usually begins in the gut and olfactory mucosa, spreading to the brain via the vagus and olfactory nerves, by a prion-like mechanism. A causal relationship has not been established, but gut dysbiosis is prevalent in PD and may lead to intestinal inflammation and barrier dysfunction. Additionally, epidemiological data indicate a link between inflammatory bowel diseases and PD. Calprotectin and zonulin are markers of intestinal inflammation and barrier permeability, respectively. We evaluated their serum and fecal levels in 22 patients with sporadic PD and 16 unmatched healthy controls. Mean calprotectin was higher in PD, both in serum (14.26 mcg/ml ± 4.50 vs. 5.94 mcg/ml ± 3.80, p = 0.0125) and stool (164.54 mcg/g ± 54.19 vs. 56.19 mcg/g ± 35.88, p = 0.0048). Mean zonulin was also higher in PD serum (26.69 ng/ml ± 3.55 vs. 19.43 ng/ml ± 2.56, p = 0.0046) and stool (100.19 ng/ml ± 28.25 vs. 37.3 ng/ml ± 13.26, p = 0.0012). Calprotectin was above the upper reference limit in 19 PD serums and 6 controls (OR = 10.56, 95% CI = 2.17–51.42, p = 0.0025) and in 20 PD stool samples and 4 controls (OR = 30, 95% CI = 4.75–189.30, p = 0.000045). Increased zonulin was found only in the stool samples of 8 PD patients. Despite the small sample size, our findings are robust, complementing and supporting other recently published results. The relation between serum and fecal calprotectin and zonulin levels and sporadic PD warrants further investigation in larger cohorts.

Limited Bacterial Removal in Full-Scale Stormwater Biofilters as Evidenced by Community Sequencing Analysis.

In urban areas, untreated stormwater runoff can pollute downstream surface waters. To intercept and treat runoff, low-impact or "green infrastructure" approaches such as using biofilters are adopted. Yet, actual biofilter pollutant removal is poorly understood; removal is often studied in laboratory columns, with variable removal of viable and culturable microbial cell numbers including pathogens. Here, to assess bacterial pollutant removal in full-scale planted biofilters, stormwater was applied, unspiked or spiked with untreated sewage, in simulated storm events under transient flow conditions, during which biofilter influents versus effluents were compared. Based on microbial biomass, sequences of bacterial community genes encoding 16S rRNA, and gene copies of the human fecal marker HF183 and of the Enterococcus spp. marker Entero1A, removal of bacterial pollutants in biofilters was limited. Dominant bacterial taxa were similar for influent versus effluent aqueous samples within each inflow treatment of either spiked or unspiked stormwater. Bacterial pollutants in soil were gradually washed out, albeit incompletely, during simulated storm flushing events. In post-storm biofilter soil cores, retained influent bacteria were concentrated in the top layers (0-10 cm), indicating that the removal of bacterial pollutants was spatially limited to surface soils. To the extent that plant-associated processes are responsible for this spatial pattern, treatment performance might be enhanced by biofilter designs that maximize influent contact with the rhizosphere.

The Addition of Other Fecal Biomarkers Does Not Improve the Diagnostic Accuracy of Immunochemical Fecal Occult Blood Test Alone in a Colorrectal Cancer Screening Cohort

Background: Screening with fecal occult blood test reduces colorectal cancer (CRC) incidence and mortality, and is currently implemented in most countries. However, around 40% of screening colonoscopies are normal. Thus, strategies to avoid these colonoscopies are highly necessary. Adding other fecal biomarkers, such as fecal calprotectin (FC), lactoferrin, and transferrin may be useful, but evidence is scarce.Aims: To evaluate the diagnostic accuracy of fecal occult blood immunochemical test (FIT), FC, and a one-step combo card test for the simultaneous semi-qualitative detection of human hemoglobin (hHb), transferrin (hTf), calprotectin (hCp) and lactoferrin (hLf) in a CRC screening program population.Methods: Single-center, prospective observational study, enrolling patients included in a CRC screening program, referred for a colonoscopy due to a positive FIT test. Participants collected a stool sample prior to bowel preparation, and FIT, FC and the combo semi-qualitative tests were performed on the sample. Sensitivity, specificity, positive and negative predictive values and area under receiver operator curve (AUC) for diagnosis of advanced neoplasia, advanced adenoma and CRC were estimated for each biomarker and their combinations. The primary endpoint of the study was to assess whether these biomarkers could improve the diagnostic accuracy of FIT alone.Results: 336 consecutive patients (64% males) were recruited. Advanced neoplasia was found in 129/336 (38.4%) patients, and of these, 22/336 (6.5%) were diagnosed of CRC. 153/336 (45.5%) colonoscopies were completely normal. The AUC for the diagnosis of advanced neoplasia were 0.725 (95%CI 0.665–0.784) for FIT, 0.477 (95%CI 0.413–0.541) for FC and 0.732 (95%CI 0.674–0.791) for the combination of both (FIT + FC) quantitative tests. The AUCs for the combo test were 0.70 (95%CI 0.641–0.760) for hHb, 0.625 (95%CI 0.562–0.698) for hTf, 0.532 (95%CI 0.469–0.595) for hCp, 0.531 (95%CI 0.466–0.595 ) for hLf and 0.681 (95%CI 0.620–0.741) for the combination of the four biomarkers.Conclusion: In average-risk population, FIT appears to be the best fecal marker for the diagnosis of CRC and advanced adenoma. None of the other biomarkers explored or their combinations provided a better diagnostic accuracy. Only hTF showed an acceptable diagnostic accuracy. FC and hLF were not useful in this setting.

Sources and Risk Factors for Nitrate and Microbial Contamination of Private Household Wells in the Fractured Dolomite Aquifer of Northeastern Wisconsin.

Background:Groundwater quality in the Silurian dolomite aquifer in northeastern Wisconsin, USA, has become contentious as dairy farms and exurban development expand.Objectives:We investigated private household wells in the region, determining the extent, sources, and risk factors of nitrate and microbial contamination.Methods:Total coliforms, Escherichia coli, and nitrate were evaluated by synoptic sampling during groundwater recharge and no-recharge periods. Additional seasonal sampling measured genetic markers of human and bovine fecal-associated microbes and enteric zoonotic pathogens. We constructed multivariable regression models of detection probability (log-binomial) and concentration (gamma) for each contaminant to identify risk factors related to land use, precipitation, hydrogeology, and well construction.Results:Total coliforms and nitrate were strongly associated with depth-to-bedrock at well sites and nearby agricultural land use, but not septic systems. Both human wastewater and cattle manure contributed to well contamination. Rotavirus group A, Cryptosporidium, and Salmonella were the most frequently detected pathogens. Wells positive for human fecal markers were associated with depth-to-groundwater and number of septic system drainfield within . Manure-contaminated wells were associated with groundwater recharge and the area size of nearby agricultural land. Wells positive for any fecal-associated microbe, regardless of source, were associated with septic system density and manure storage proximity modified by bedrock depth. Well construction was generally not related to contamination, indicating land use, groundwater recharge, and bedrock depth were the most important risk factors.Discussion:These findings may inform policies to minimize contamination of the Silurian dolomite aquifer, a major water supply for the U.S. and Canadian Great Lakes region. https://doi.org/10.1289/EHP7813

Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn’s disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

P214 Faecal S100A12 as a non-invasive marker of inflammatory activity in pediatric Inflammatory Bowel Disease

Abstract Background Calgranulin-C (S100A12) is a new faecal marker of inflammation that is potentially more specific for Inflammatory Bowel Disease (IBD) than calprotectin, since it is only released by activated granulocytes. In recent years it has been confirmed that the S100A12 has comparable sensitivity and specificity to fecal calprotectin (FC) in adult patients with IBD. The aim of our study was to evaluate concentration of faecal S100A12 and calprotectin (FC) to see which of the two tests best correlated to inflammation in IBD children. Methods Between September 2019 and March 2020, we prospectively enrolled all IBD pediatric patients, both Crohn’s Disease (CD) and Ulcerative Colitis (UC). Blood and faecal samples were collected in order to evaluate serological markers of inflammation, faecal S100A12A and FC. S100A12 and FC were determined by enzyme-linked immunosorbent assay (ELISA). Results One hundred seventeen consecutive children, 46 (39%) with CD and 71 (61%) with UC were enrolled in the study. The mean age was 14.6 years (range:5–18), 44% female. Twenty three children were in clinical relapse (20%). No significant differences in S100 A12A levels were found between the UC and the CD groups (mean ±ds 25 ±32mcg/ml vs 34 ±27 mcg/ml respectively, p=0.22).In the UC group we found a statistically significant correlation of both calprotectin and S100A12 with CRP (r=0.253, p=0.044 and r=0.252, p=0.040, respectively). In CD group we found that both calprotectin and S100A12 correlated with hemoglobin (r= -0.343, p=0,024; r=-0.401, p 0.008 respectively), hematocrit (r=-0.361, p=0,046; r=-0.434, p=0.015, respectively), fibrinogen (r=0.499, p&amp;lt; 0,001; r=0.325, p =0.038, respectively), and white blood cells count (r=0.309, p=0.044; r=0.394, p=0.021, respectively). Moreover, in CD group, FC correlated with CRP (r=0.431, p=0.004) and erythrocyte sedimentation rate (r=0.430, p=0.004). Finally, S100A12 correlated with platelet count both in CD and UC group (r=0.351, p=0.021and r=0.254, p=0.038, respectively) IBD children in clinical relapse had higher values ​​of S100A12 and FC than patients in remission (66±47 mcg/ml vs 43±42 mcg/ml, p=0.05 and 260±192 mg/Kg vs 166±169 mg/Kg, p=0.046, respectively) Conclusion Our preliminary data show that both faecal S100A12 and FC are useful non-invasive biomarkers which reflect inflammatory activity of IBD children. Our future aim is to evaluate the correlation of S100A12 and endoscopic finding in order to further clarify its role in the diagnosis and the management of pediatric IBD.

Short- and Branched-Chain Fatty Acids as Fecal Markers for Microbiota Activity in Vegans and Omnivores.

A vegan diet could impact microbiota composition and bacterial metabolites like short-chain (SCFA) and branched-chain fatty acids (BCFA). The aim of this study was to compare the concentrations of SCFA, BCFA, ammonia, and fecal pH between vegans and omnivores. In this cross-sectional study (vegans n = 36; omnivores n = 36), microbiota composition, fecal SCFA, BCFA, and ammonia concentrations and pH were analyzed in complete stool samples. A random forest regression (RFR) was used to identify bacteria predicting SCFA/BCFA concentrations in vegans and omnivores. No significant differences in SCFA and BCFA concentrations were observed between vegans and omnivores. Fecal pH (p = 0.005) and ammonia concentration (p = 0.01) were significantly lower in vegans than in omnivores, while fiber intake was higher (p < 0.0001). Shannon diversity was higher in omnivores compared to vegans on species level (p = 0.04) only. In vegans, a cluster of Faecalibacterium prausnitzii, Prevotella copri, Dialister spp., and Eubacterium spp. was predictive for SCFA and BCFA concentrations. In omnivores, Bacteroides spp., Clostridium spp., Ruminococcus spp., and Prevotella copri were predictive. Though SCFA and BCFA did not differ between vegans and omnivores, the results of the RFR suggest that bacterial functionality may be adapted to varying nutrient availability in these diets.

Influence of energy supplementation on associative effects in Nellore bulls on a tropical pasture during the rainy season

The objective of this study was to evaluate the influence of energy supplementation on associative effects between forage and concentrate supplements and on the performance of beef cattle on a tropical pasture during the rainy season. Twenty-eight Nellore bulls averaging 19 months of age and 325.2 ± 4.1 kg were allotted to a completely randomized design and distributed into four paddocks of two hectares each with a tropical pasture for 84 d. The treatments consisted of bulls on Urochloa brizantha cv. Xaraés pasture without concentrate supplementation or bulls on Urochloa brizantha cv. Xaraés pasture receiving concentrate supplementation at 15 (S15), 30 (S30) or 45% (S45) of the total digestible nutrients (TDN) requirement All bulls had ad libitum access to mineral supplementation. The amount and chemical composition of the supplement were adjusted every 28 d. Forage and supplement intakes were evaluated in all animals using fecal markers. Crude protein: digestible organic matter ratio decreased with supplementation; consequently, the imbalance between dietary protein and energy increased. Forage intake decreased with increasing supplementation. The substitution rates of pasture for supplementary feed were 0.14, 0.33, and 0.46 for bulls from S15, S30, and S45 treatments, respectively. However, the apparent DM digestibility increased linearly with supplementation level. Supplementation improved the assimilation of ammonia-N in the rumen. Energy supplementation for Nellore bulls on tropical pastures during the rainy season provides excess energy relative to protein, resulting in a substitution effect of supplement intake on forage intake. Moreover, energy supplementation does not improve body weight gain. Protein sources should be added to supplements for balancing protein and energy levels, thereby reducing a likely substitution effect.

Seasonal dynamics in the number and composition of coliform bacteria in drinking water reservoirs

Worldwide, surface waters like lakes and reservoirs are one of the major sources for drinking water production, especially in regions with water scarcity. In recent years, increased numbers of coliform bacteria have been observed in these surface waters. In our monitoring study we analyzed two drinking water reservoirs (Klingenberg and Kleine Kinzig Reservoir) over a two-year period in 2018 and 2019. We detected high numbers of coliform bacteria up to 2.4 × 104 bacteria per 100 ml during summer months, representing an increase of four orders of magnitude compared to winter. Diversity decreased to one or two species that dominated the entire water body, namely Enterobacter asburiae and Lelliottia spp., depending on the reservoir. Interestingly, the same, very closely related strains have been found in several reservoirs from different regions. Fecal indicator bacteria Escherichia coli and enterococci could only be detected in low concentrations. Furthermore, fecal marker genes were not detected in the reservoir, indicating that high concentrations of coliform bacteria were not due to fecal contamination. Microbial community revealed Frankiales and Burkholderiales as dominant orders. Enterobacterales, however, only had a frequency of 0.04% within the microbial community, which is not significantly affected by the extreme change in coliform bacteria number. Redundancy analysis revealed water temperature, oxygen as well as nutrients and metals (phosphate, manganese) as factors affecting the dominant species. We conclude that this sudden increase of coliform bacteria is an autochthonic process that can be considered as a mass proliferation or “coliform bloom” within the reservoir. It is correlated to higher water temperatures in summer and is therefore expected to occur more frequently in the near future, challenging drinking water production.

Evaluation of private well contaminants in an underserved North Carolina community

On-site sewage treatment systems can be an important source of antibiotic resistant bacteria and organic micropollutants into adjacent groundwater. Due to the frequent proximity of private wells to septic systems, this contamination is a concern to communities that do not have access to public municipal services. In both rural and urban environments, low-income communities, indigenous communities and those of color are disproportionately affected by well contamination. The objective of this study was to assess well water quality in an underserved North Carolina community by performing a comprehensive evaluation of microbial and organic micropollutant occurrence and determining possible sources of contamination. Well water, septic tanks, and adjacent municipal water were sampled. Culture- and molecular biology-based microbial analysis and non-targeted, high resolution mass spectrometry chemical analysis were conducted to assess water quality in comparison to nearby municipal water. Three of thirteen homes had between 1 and 6.3 CFUs/100 mL of E. coli and two homes had fecal bacteria resistant to antibiotics in their well water. The water of four homes showed concentrations of the artificial sweetener sucralose, a wastewater tracer, higher than the municipal water (range ~ 60–1500 ng L−1). The human-specific HF183 fecal marker was detected in 79% of the wells tested. The presence of pharmaceuticals and personal care products in four home wells, along with the presence of pesticides and insecticides in two homes, suggest possible contamination from septic tanks and lawn care runoff. The implications of this work highlight the necessity of wider scale contaminant evaluation of well water.

30 The Effect of Creep Feed Composition and Form on Pre- and Post-weaning Growth Performance of Pigs and the Utilization of Low-quality Nursery Diets

Abstract Fifty-six litters standardized to 12 piglets from first-parity sows were used to determine the effects of creep and nursery diet compositions on pre- and post-weaning pig growth performance. At three days of age, litters (initial BW 2.31±0.61kg) were assigned to one of four creep feeding regimens (n=14): [1] commercial creep feed (COM), [2] liquid milk replacer (LMR), [3] pelleted milk replacer (PMR), or [4] no creep feed (NO); creep feeds contained 1.0% brilliant blue as a fecal marker. Fecal swabs were collected every 3±1 days to identify piglets that regularly consumed creep feed. At weaning (18±1 days of age), six pigs per litter that consumed creep feed were placed on either a HIGH- (contained highly digestible animal proteins) or LOW- (contained corn and soybean meal as the main protein sources) quality nursery diet (n = 7) in a three-phase feeding program over 38 days. The LMR disappeared at the greatest rate (37.7 g/pig/d; DM-basis) versus COM and PMR (10.8±1.5 g/pig/d; P &amp;lt; 0.001). Litters that received LMR had the greatest proportion of pigs with blue fecal swabs between study days 4 and 15 (85.0 vs 59.0±0.4%; P &amp;lt; 0.05) and LMR piglets had greater BW at weaning versus all other treatments (6.32, 6.02, 5.92, 5.67±0.14 kg, for LMR, COM, NO, and PMR, respectively; P &amp;lt; 0.001). Over the entire nursery period, pigs that received LOW diets had reduced ADG (399 vs 485±42 g; P &amp;lt; 0.001), ADFI (520 vs 595±37 g; P&amp;lt; 0.001), G:F (0.77 vs 0.82±0.03; P &amp;lt; 0.01), and BW at the end of the nursery period (21.2 vs 24.4±1.6 kg; P &amp;lt; 0.001), with no carryover effects of creep feeding regimen. Providing supplemental nutrition during the suckling period via LMR improved pig body weight at weaning, but did not improve post-weaning growth performance, regardless of nursery diet quality.

Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review.

BACKGROUNDMucosal healing (MH) has emerged as a key therapeutic target in inflammatory bowel disease (IBD), and achievement of this goal is documented by endoscopy with biopsy. However, colonoscopy is burdensome and invasive, and substitution with an accurate noninvasive biomarker is desirable.AIMTo summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients.METHODSWe conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD. The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH.RESULTSWe screened 1301 articles, retrieved 46 manuscripts and included 23 articles for full-text analysis. The majority of the included manuscripts referred to fecal markers (12/23), followed by circulatory markers (8/23); only 3/23 of the included manuscripts investigated combined markers (serum and/or fecal markers). Fecal calprotectin (FC) was the most investigated fecal marker for assessing MH. In ulcerative colitis, for cutoff levels ranging between 58 mcg/g and 490 mcg/g, the sensitivity was 89.7%-100% and the specificity was 62%-93.3%. For Crohn’s disease, the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g (sensitivity 50%-95.9% and specificity 52.3%-100%). The best performance for a serum marker was observed for the endoscopic healing index, which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.CONCLUSIONSeveral promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.

Faecal microbial metabolites of proteolytic and saccharolytic fermentation in relation to degree of insulin resistance in adult individuals.

The gut microbiota may affect host metabolic health through microbial metabolites. The balance between the production of microbial metabolites by saccharolytic and proteolytic fermentation may be an important determinant of metabolic health. Amongst the best-studied saccharolytic microbial metabolites are the short-chain fatty acids acetate, propionate and butyrate. However, human data on the role of other microbial fermentation by-products in metabolic health are greatly lacking. Therefore, we compared in a cross-sectional study the faecal microbial metabolites (caproate, lactate, valerate, succinate, and the branched-chain fatty acids (BCFA) (isobutyrate, isovalerate)) between insulin sensitive (homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-IR<1.85, IS) and insulin resistant (HOMA-IR>1.85, IR) individuals. Additionally, we assessed the relationships between faecal metabolites and markers of metabolic health including fasting glucose, insulin, free fatty acids, insulin resistance (HOMA-IR) and fasting substrate oxidation in 86 individuals with a wide range of body mass index. Faecal metabolite concentrations did not significantly differ between IS and IR. Furthermore, there were no associations between microbial metabolites and metabolic health markers, except for a slight positive association of isovalerate with carbohydrate oxidation (E%, std β 0.194, P=0.011) and fat oxidation (E%, std β -0.075, P=0.047), also after adjustment for age, sex and BMI. In summary, faecal caproate, lactate, valerate, succinate, and BCFA (isobutyrate, isovalerate) were not different between IR and IS individuals, nor was there any association between these faecal metabolites and parameters of metabolic health. Further human intervention studies are warranted to investigate the role of these microbially-derived fermentation products and their kinetics in metabolic health and insulin sensitivity.

Short-chain fatty acids and intestinal inflammation in multiple sclerosis: modulation of female susceptibility by microbial products?

BackgroundMultiple Sclerosis (MS) is an autoimmune-mediated disease of the central nervous system. Experimental data suggest a role of intestinal microbiota and microbial products such as short-chain fatty acids (SCFAs) in the pathogenesis of MS. A recent clinical study reported beneficial effects (mediated by immunomodulatory mechanisms) after oral administration of the SCFA propionate in MS patients. Based on available evidence, we investigated whether SCFAs and the fecal inflammation marker calprotectin are altered in MS.Methods76 subjects (41 patients with relapsing–remitting MS and 35 age-matched controls) were investigated in this case–control study. All subjects underwent clinical assessment with established clinical scales and provided fecal samples for a quantitative analysis of fecal SCFA and fecal calprotectin concentrations. Fecal markers were compared between MS patients and controls, and were analyzed for an association with demographic as well as clinical parameters.ResultsMedian fecal calprotectin concentrations were within normal range in both groups without any group-specific differences. Fecal SCFA concentrations showed a non-significant reduction in MS patients compared to healthy subjects. Female subjects showed significantly reduced SCFA concentrations compared to male subjects.ConclusionsIn our cohort of MS patients, we found no evidence of an active intestinal inflammation. Yet, the vast majority of the investigated MS patients was under immunotherapy which might have affected the outcome measures. The sex-associated difference in fecal SCFA concentrations might at least partially explain female predominance in MS. Large-scale longitudinal studies including drug-naïve MS patients are required to determine the role of SCFAs in MS and to distinguish between disease-immanent effects and those caused by the therapeutic regime.

Alterations in the human oral and gut microbiomes and lipidomics in COVID-19

ObjectiveTo characterise the oral microbiome, gut microbiome and serum lipid profiles in patients with active COVID-19 and recovered patients; evaluate the potential of the microbiome as a non-invasive biomarker for...