Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation.

BACKGROUND: Patients with pelvic malignancies often receive radiosensitising chemotherapy with radiotherapy to improve survival; however, this is at the expense of increased normal tissue toxicity, particularly in elderly patients. Here, we explore if an alternative, low-cost, and non-toxic approach can achieve radiosensitisation in mice transplanted with human bladder cancer cells. Other investigators have shown slower growth of transplanted tumours in mice fed high-fibre diets. We hypothesised that mice fed a high-fibre diet would have improved tumour control following ionising radiation (IR) and that this would be mediated through the gut microbiota. RESULTS: We investigated the effects of four different diets (low-fibre, soluble high-fibre, insoluble high-fibre, and mixed soluble/insoluble high-fibre diets) on tumour growth in immunodeficient mice implanted with human bladder cancer flank xenografts and treated with ionising radiation, simultaneously investigating the composition of their gut microbiomes by 16S rRNA sequencing. A significantly higher relative abundance of Bacteroides acidifaciens was seen in the gut (faecal) microbiome of the soluble high-fibre group, and the soluble high-fibre diet resulted in delayed tumour growth after irradiation compared to the other groups. Within the soluble high-fibre group, responders to irradiation had significantly higher abundance of B. acidifaciens than non-responders. When all mice fed with different diets were pooled, an association was found between the survival time of mice and relative abundance of B. acidifaciens. The gut microbiome in responders was predicted to be enriched for carbohydrate metabolism pathways, and in vitro experiments on the transplanted human bladder cancer cell line suggested a role for microbial-generated short-chain fatty acids and/or other metabolites in the enhanced radiosensitivity of the tumour cells. CONCLUSIONS: Soluble high-fibre diets sensitised tumour xenografts to irradiation, and this phenotype was associated with modification of the microbiome and positively correlated with B. acidifaciens abundance. Our findings might be exploitable for improving radiotherapy response in human patients.

Prebiotics Inhibit Proteolysis by Gut Bacteria in a Host Diet-Dependent Manner: a Three-Stage Continuous In Vitro Gut Model Experiment.

Dietary protein residue can result in microbial generation of various toxic metabolites in the gut, such as ammonia. A prebiotic is "a substrate that is selectively utilised by host microorganisms conferring a health benefit" (G. R. Gibson, R. Hutkins, M. E. Sanders, S. L. Prescott, et al., Nat Rev Gastroenterol Hepatol 14:491-502, 2017, https://doi.org/10.1038/nrgastro.2017.75). Prebiotics are carbohydrates that may have the potential to reverse the harmful effects of gut bacterial protein fermentation. Three-stage continuous colonic model systems were inoculated with fecal samples from omnivore and vegetarian volunteers. Casein (equivalent to 105 g protein consumption per day) was used within the systems as a protein source. Two different doses of inulin-type fructans (Synergy1) were later added (equivalent to 10 g per day in vivo and 15 g per day) to assess whether this influenced protein fermentation. Bacteria were enumerated by fluorescence in situ hybridization with flow cytometry. Metabolites from bacterial fermentation (short-chain fatty acid [SCFA], ammonia, phenol, indole, and p-cresol) were monitored to further analyze proteolysis and the prebiotic effect. A significantly higher number of bifidobacteria was observed with the addition of inulin together with reduction of Desulfovibrio spp. Furthermore, metabolites from protein fermentation, such as branched-chain fatty acids (BCFA) and ammonia, were significantly lowered with Synergy1. Production of p-cresol varied among donors, as we recognized four high producing models and two low producing models. Prebiotic addition reduced its production only in vegetarian high p-cresol producers.IMPORTANCE Dietary protein levels are generally higher in Western populations than in the world average. We challenged three-stage continuous colonic model systems containing high protein levels and confirmed the production of potentially harmful metabolites from proteolysis, especially replicates of the transverse and distal colon. Fermentations of proteins with a prebiotic supplementation resulted in a change in the human gut microbiota and inhibited the production of some proteolytic metabolites. Moreover, we observed both bacterial and metabolic differences between fecal bacteria from omnivore donors and vegetarian donors. Proteins with prebiotic supplementation showed higher Bacteroides spp. and inhibited Clostridium cluster IX in omnivore models, while in vegetarian modes, Clostridium cluster IX was higher and Bacteroides spp. lower with high protein plus prebiotic supplementation. Synergy1 addition inhibited p-cresol production in vegetarian high p-cresol-producing models while the inhibitory effect was not seen in omnivore models.

Real-time automated diagnosis of precancerous lesions and early esophageal squamous cell carcinoma using a deep learning model (with videos).

BACKGROUND AND AIMS: We developed a system for computer-assisted diagnosis (CAD) for real-time automated diagnosis of precancerous lesions and early esophageal squamous cell carcinomas (ESCCs) to assist the diagnosis of esophageal cancer. METHODS: A total of 6473 narrow-band imaging (NBI) images, including precancerous lesions, early ESCCs, and noncancerous lesions, were used to train the CAD system. We validated the CAD system using both endoscopic images and video datasets. The receiver operating characteristic curve of the CAD system was generated based on image datasets. An artificial intelligence probability heat map was generated for each input of endoscopic images. The yellow color indicated high possibility of cancerous lesion, and the blue color indicated noncancerous lesions on the probability heat map. When the CAD system detected any precancerous lesion or early ESCCs, the lesion of interest was masked with color. RESULTS: The image datasets contained 1480 malignant NBI images from 59 consecutive cancerous cases (sensitivity, 98.04%) and 5191 noncancerous NBI images from 2004 cases (specificity, 95.03%). The area under curve was 0.989. The video datasets of precancerous lesions or early ESCCs included 27 nonmagnifying videos (per-frame sensitivity 60.8%, per-lesion sensitivity, 100%) and 20 magnifying videos (per-frame sensitivity 96.1%, per-lesion sensitivity, 100%). Unaltered full-range normal esophagus videos included 33 videos (per-frame specificity 99.9%, per-case specificity, 90.9%). CONCLUSIONS: A deep learning model demonstrated high sensitivity and specificity for both endoscopic images and video datasets. The real-time CAD system has a promising potential in the near future to assist endoscopists in diagnosing precancerous lesions and ESCCs.

Prebiotic Supplementation of In Vitro Fecal Fermentations Inhibits Proteolysis by Gut Bacteria, and Host Diet Shapes Gut Bacterial Metabolism and Response to Intervention.

Metabolism of protein by gut bacteria is potentially detrimental due to the production of toxic metabolites, such as ammonia, amines, p-cresol, and indole. The consumption of prebiotic carbohydrates results in specific changes in the composition and/or activity of the microbiota that may confer benefits to host well-being and health. Here, we have studied the impact of prebiotics on proteolysis within the gut in vitro Anaerobic stirred batch cultures were inoculated with feces from omnivores (n = 3) and vegetarians (n = 3) and four protein sources (casein, meat, mycoprotein, and soy protein) with and without supplementation by an oligofructose-enriched inulin. Bacterial counts and concentrations of short-chain fatty acids (SCFA), ammonia, phenol, indole, and p-cresol were monitored during fermentation. Addition of the fructan prebiotic Synergy1 increased levels of bifidobacteria (P = 0.000019 and 0.000013 for omnivores and vegetarians, respectively). Branched-chain fatty acids (BCFA) were significantly lower in fermenters with vegetarians' feces (P = 0.004), reduced further by prebiotic treatment. Ammonia production was lower with Synergy1. Bacterial adaptation to different dietary protein sources was observed through different patterns of ammonia production between vegetarians and omnivores. In volunteer samples with high baseline levels of phenol, indole, p-cresol, and skatole, Synergy1 fermentation led to a reduction of these compounds.IMPORTANCE Dietary protein intake is high in Western populations, which could result in potentially harmful metabolites in the gut from proteolysis. In an in vitro fermentation model, the addition of prebiotics reduced the negative consequences of high protein levels. Supplementation with a prebiotic resulted in a reduction of proteolytic metabolites in the model. A difference was seen in protein fermentation between omnivore and vegetarian gut microbiotas: bacteria from vegetarian donors grew more on soy and Quorn than on meat and casein, with reduced ammonia production. Bacteria from vegetarian donors produced less branched-chain fatty acids (BCFA).

Supplemental Vitamin B-12 Enhances the Neural Response to Sensory Stimulation in the Barrel Cortex of Healthy Rats but Does Not Affect Spontaneous Neural Activity.

BACKGROUND: Although vitamin B-12 (B-12) is known to contribute to the structural and functional development of the brain, it is unclear if B-12 supplementation has any beneficial effect in healthy populations in terms of enhanced neurologic status of the brain or improved cognitive function. OBJECTIVES: We investigated the effect of dietary supplementation of B-12 on the cortical neural activity of well-nourished young adult rats and tested the hypothesis that B-12 supplementation in healthy rats may reduce sensory-evoked neural activity due to enhanced inhibition. METHODS: Female Lister Hooded rats weighing 190-265 g (2-4 mo old) were included in the study. The experimental group was fed with B-12 (cyanocobalamin)-enriched water at a concentration of 1 mg/L, and the control (CON) group with tap water for 3 wk. Animals were then anesthetized and cortical neural responses to whisker stimulation were recorded in vivo through the use of a multichannel microelectrode, from which local field potentials (LFPs) were extracted. RESULTS: Somatosensory-evoked LFP was 25% larger in the B-12 group (4.13 ± 0.24 mV) than in the CON group (3.30 ± 0.21 mV) (P = 0.02). Spontaneous neural activity did not differ between groups; frequency spectra at each frequency bin of interest did not pass the cluster-forming threshold at the 5% significance level. CONCLUSIONS: These findings do not provide evidence supporting the hypothesis of decreased neural activity due to B-12 supplementation. As the spontaneous neural activity was unaffected, the increase in somatosensory-evoked LFP may be due to enhanced afferent signal reaching the barrel cortex from the whisker pad, indicating that B-12-supplemented rats may have enhanced sensitivity to sensory stimulation compared with the CON group. We suggest that this enhancement might be the result of lowered sensory threshold, although the underlying mechanism has yet to be elucidated.

Apigenin Alleviates Myocardial Reperfusion Injury in Rats by Downregulating miR-15b.

BACKGROUND We investigated whether apigenin could mitigate myocardial reperfusion injury in rats, and a possible mechanism was proposed. MATERIAL AND METHODS The I-R injury model was established in rats along with a sham group as control, and the expressions of microRNA-15b (miR-15b), JAK2, and p-JAK2 in the myocardia of the 2 groups were detected. Apoptosis and reactive oxygen species (ROS) were also detected. Rats in the I-R injury model were divided into 3 groups in vivo: the 1I-R group, the 2I-R+solvent group, and the 3I-R+apigenin group. Expression of miR-15b, JAK2, p-JAK2, STAT3, and p-STAT3 in the myocardia of the 3 groups were detected. ROS content, apoptosis, MDA content, SOD, and CAT activities were detected. Rat myocardial H9C2 cells were cultured in vitro and divided into 5 treatment groups in vitro; expressions of miR-15b, JAK2, p-JAK2, STAT3, and p-STAT3 in H9C2 cells were detected, and the apoptosis and ROS content were detected by flow cytometry. RESULTS We found that the increased miR-15b expression during myocardial I-R injury in rats downregulated the expression of JAK2 and activity of the JAK2-STAT3 pathway, promoted myocardial apoptosis and ROS production, and aggravated myocardial I-R injury. Apigenin treatment can downregulate miR-15b expression, increase the expression of JAK2 and the activity of JAK2-STAT3 pathway, reduce myocardial apoptosis and ROS production, and alleviate myocardial I-R injury. CONCLUSIONS Api treatment downregulated the expression of miR-15b and upregulated the expression of JAK2 and the activity of the JAK2-STAT3 pathway, thereby alleviating myocardial I-R injury, cardiomyocyte apoptosis, and ROS production in vitro.

Synthesis and Monkey-PET Study of (R)- and (S)-18F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive in Vivo Kinetics.

This study describes an effective strategy to improve pharmacokinetics of Aß imaging agents, offering a novel class of (R)- and (S)-18F-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward Aß aggregates with Ki values ranging from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution, and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20. Notably, (S)-[18F]28 possessed high binding potency (Ki = 7.6 nM) and exceptional brain kinetics (9.46% ID/g at 2 min, brain2min/brain60min = 27.8) that is superior to well-established [18F]AV45. The excellent pharmacokinetics and low nonspecific binding of (S)-[18F]28 were testified by dynamic PET/CT scans in monkey brains. In addition, (S)-[18F]28 clearly labeled Aß plaques both in vitro and ex vivo. These results might qualify (S)-[18F]28 to detect Aß plaques with high signal-to-noise ratio.

Highly Regioselective Radical Amination of Allenes: Direct Synthesis of Allenamides and Tetrasubstituted Alkenes.

The first controllable, regioselective radical amination of allenes with N-fluoroarylsulfonimide is described to proceed under very mild reaction conditions. With this methodology, a general and straightforward route for the synthesis of both allenamides and fluorinated tetrasubstituted alkenes was realized from a wide range of terminal and internal allenes.

A Case Report of Malignant Perivascular Epithelioid Cell Tumors of the Uterus and Literature Review.

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors originating from perivascular epithelioid cells. In gynecological system, the uterus is one of the most common sites affected by PEComas. Most PEComas are benign, and patients usually have a good prognosis. However, malignant uterus PEComa is rare, and better comprehensive epidemiological investigations are needed. To date, there are a few reported cases of uterus PEComa. We herein report a rare case of malignant PEComa occurred in the uterine corpus and cervix, possibly accompanied by pulmonary lymphangioleiomyomatosis (PLAM). In addition, 55 cases of malignant uterus PEComa were picked out and collected in the data base of PubMed and Medline. On the one hand, the age of onset, population distribution, clinical manifestations, metastatic sites and routes of metastasis were analysed. On the other hand, a summary of the epidemiology, pathogenesis, diagnosis, and treatments of uterus PEComa was given.

Effects of micro- and nano-plastics on growth, antioxidant system, DMS, and DMSP production in Emiliania huxleyi.

Due to the potential impacts of microplastics (MPs) and nanoplastics (NPs) on algal growth and thereby affect the climate-relevant substances, dimethylsulfoniopropionate (DMSP) and dimethyl sulfide (DMS), we studied the polystyrene (PS) MPs and NPs of 1 µm and 80 nm impacts on the growth, chlorophyll content, reactive oxygen species (ROS), antioxidant enzyme activity, and DMS/DMSP production in Emiliania huxleyi. E. huxleyi is a prominent oceanic alga that plays a key role in DMS and DMSP production. The results revealed that high concentrations of MPs and NPs inhibited the growth, carotenoid (Car), and Chl a concentrations of E. huxleyi. However, short-time exposure to low concentrations of PS MPs and NPs stimulated the growth of E. huxleyi. Furthermore, high concentrations of MPs and NPs resulted in an increase in the superoxide anion radical (O2.-) production rate and a decrease in the malondialdehyde (MDA) content compared with the low concentrations. Exposure to MPs and NPs at 5 mg L-1 induced superoxide dismutase (SOD) activity as a response to scavenging ROS. High concentrations of MPs and NPs significantly inhibited the production of DMSP and DMS. The findings of this study support the potential ecotoxicological impacts of MPs and NPs on algal growth, antioxidant system, and dimethylated sulfur compounds production, which maybe potentially impact the global climate.

Intrinsic capacity decline as a predictor of functional disability in the elderly: A systematic review and meta-analysis.

OBJECTIVES: To examine the predictive value of intrinsic capacity decline on functional disability among the elderly. DESIGN: Meta-analysis. METHODS: PubMed, EMBASE, Web of Science, The Cochrane Library, Wanfang Database, China Knowledge Resource Integrated Database (CNKI), Weipu Database (VIP), and Chinese Biomedical Database (CBM) were searched for relevant studies published from the inception until June 1, 2024. Stata 17.0 software was used to perform the meta-analysis. The methodological quality was evaluated using the Newcastle Ottawa Scale. The overall quality of evidence used GRADE guidelines to assess. A study protocol was registered in PROSPERO (CRD42023475461). RESULTS: The meta-analysis included 8 cohort studies including 9744 elderly people. Functional disability including ADL disability (n = 6) and IADL disability (n = 7). The results showed that intrinsic capacity decline could predict ADL disability (HR = 1.08, 95 %CI 1.04-1.12; I2 = 98.2 %, P < 0.001) and IADL disability (HR = 1.11, 95 %CI 1.05-1.17; I2 = 96.4 %, P < 0.001). The overall risk of bias was low. And the grade of evidence that assessed by GRADE guidelines was rated as moderate. CONCLUSIONS: Intrinsic capacity decline is a predictor of functional disability in the elderly. Therefore, screening intrinsic capacity decline has important clinical implications for early identifying the risk of functional disability, which contributes to providing individualized interventions ahead of potential functional disability for the elderly, thereby preventing functional disability, improving the quality of life and promoting healthy aging.

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity.

BACKGROUND: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. RESULT: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. CONCLUSION: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.

Synthesis and biological evaluation of 18F-labled 2-phenylindole derivatives as PET imaging probes for ß-amyloid plaques.

A novel series of fluorinated 2-phenylindole derivatives were synthesized and evaluated as ß-amyloid imaging probes for PET. The in vitro inhibition assay demonstrated that their binding affinities for Aß(1-42) aggregates ranged from 28.4 to 1097.8 nM. One ligand was labeled with (18)F ([(18)F]1a) for its high affinity (K(i)=28.4 nM), which was also confirmed by in vitro autoradiography experiments on brain sections of transgenic mouse (C57BL6, APPswe/PSEN1, 11 months old, male). In vivo biodistribution experiments in normal mice showed that this radiotracer displayed high initial uptake (5.82±0.51% ID/g at 2 min) into and moderate washout (2.77±0.31% ID/g at 60 min) from the brain. [(18)F]1a could be developed as a promising new PET imaging probe for Aß plaques although necessary modifications are still needed.

Development and validation of a diagnostic model for AFP-negative hepatocellular carcinoma.

PURPOSE: AFP appears to be negative in about 30% of overall hepatocellular carcinoma (HCC). Our study aimed to develop a nomogram model to diagnose AFP-negative HCC (AFPN-HCC). PATIENTS AND METHODS: The training set included 294 AFPN-HCC patients, 159 healthy objects, 63 patients with chronic hepatitis B(CHB), and 64 patients with liver cirrhosis (LC). And the validation set enrolled 137 healthy controls objects, 47 CHB patients and 45 patients with LC. LASSO, univariate, and multivariable logistic regression analysis were performed to construct the model and then transformed into a visualized nomogram. The receiver operating characteristic (ROC) curves, the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were further used for validation. RESULTS: Four variables including age, PIVKA-II, platelet (PLT) counts, and prothrombin time (PT) were selected to establish the nomogram. The area under the curve (AUC) of the ROC to distinguish AFPN-HCC patients was 0.937(95% CI 0.892-0.938) in training set and 0.942(95% CI 0.921-0.963) in validation set. We also found that the model had high diagnostic value for small-size HCC (tumor size < 5 cm) (AUC = 0.886) and HBV surface antigen-positive AFPN-HCC (AUC = 0.883). CONCLUSIONS: Our model was effective for discrimination of AFPN-HCC from patients with benign liver diseases and healthy controls, and might be helpful for the diagnosis for AFPN-HCC.

Microbiome diversity protects against pathogens by nutrient blocking.

The human gut microbiome plays an important role in resisting colonization of the host by pathogens, but we lack the ability to predict which communities will be protective. We studied how human gut bacteria influence colonization of two major bacterial pathogens, both in vitro and in gnotobiotic mice. Whereas single species alone had negligible effects, colonization resistance greatly increased with community diversity. Moreover, this community-level resistance rested critically upon certain species being present. We explained these ecological patterns through the collective ability of resistant communities to consume nutrients that overlap with those used by the pathogen. Furthermore, we applied our findings to successfully predict communities that resist a novel target strain. Our work provides a reason why microbiome diversity is beneficial and suggests a route for the rational design of pathogen-resistant communities.

Synthesis and biological evaluation of novel technetium-99m labeled phenylbenzoxazole derivatives as potential imaging probes for ß-amyloid plaques in brain.

Two uncharged (99m)Tc-labeled phenylbenzoxazole derivatives were biologically evaluated as potential imaging probes for ß-amyloid plaques. The (99m)Tc and corresponding rhenium complexes were synthesized by coupling monoamine-monoamide dithiol (MAMA) and bis(aminoethanethiol) (BAT) chelating ligand via a pentyloxy spacer to phenylbenzoxazole. The fluorescent rhenium complexes 6 and 9 selectively stainined the ß-amyloid plaques on the sections of transgenic mouse, and showed high affinity for Aß((1-42)) aggregates (K(i)=11.1 nM and 14.3 nM, respectively). Autoradiography in vitro indicated that [(99m)Tc]6 clearly labeled ß-amyloid plaques on the sections of transgenic mouse. Biodistribution experiments in normal mice revealed that [(99m)Tc]6 displayed moderate initial brain uptake (0.81% ID/g at 2 min), and quickly washed out from the brain (0.25% ID/g at 60 min). The preliminary results indicate that the properties of [(99m)Tc]6 are promising, although additional refinements are needed to improve the ability to cross the blood-brain barrier.

Protein supplementation during an energy-restricted diet induces visceral fat loss and gut microbiota amino acid metabolism activation: a randomized trial.

Interactions between diet and gut microbiota are critical regulators of energy metabolism. The effects of fibre intake have been deeply studied but little is known about the impact of proteins. Here, we investigated the effects of high protein supplementation (Investigational Product, IP) in a double blind, randomised placebo-controled intervention study (NCT01755104) where 107 participants received the IP or an isocaloric normoproteic comparator (CP) alongside a mild caloric restriction. Gut microbiota profiles were explored in a patient subset (n = 53) using shotgun metagenomic sequencing. Visceral fat decreased in both groups (IP group: - 20.8 ± 23.2 cm2; CP group: - 14.5 ± 24.3 cm2) with a greater reduction (p < 0.05) with the IP supplementation in the Per Protocol population. Microbial diversity increased in individuals with a baseline low gene count (p < 0.05). The decrease in weight, fat mass and visceral fat mass significantly correlated with the increase in microbial diversity (p < 0.05). Protein supplementation had little effects on bacteria composition but major differences were seen at functional level. Protein supplementation stimulated bacterial amino acid metabolism (90% amino-acid synthesis functions enriched with IP versus 13% in CP group (p < 0.01)). Protein supplementation alongside a mild energy restriction induces visceral fat mass loss and an activation of gut microbiota amino-acid metabolism.Clinical trial registration: NCT01755104 (24/12/2012). https://clinicaltrials.gov/ct2/show/record/NCT01755104?term=NCT01755104&draw=2&rank=1 .

Modifying gut integrity and microbiome in children with severe acute malnutrition using legume-based feeds (MIMBLE): A pilot trial.

Case fatality among African children with severe acute malnutrition remains high. We report a 3-arm pilot trial in 58 Ugandan children, comparing feeds targeting disordered gastrointestinal function containing cowpea (CpF, n = 20) or inulin (InF, n = 20) with conventional feeds (ConF, n = 18). Baseline measurements of gut permeability (lactulose:mannitol ratio 1.19 ± SD 2.00), inflammation (fecal calprotectin 539.0 µg/g, interquartile range [IQR] 904.8), and satiety (plasma polypeptide YY 62.6 pmol/l, IQR 110.3) confirm gastrointestinal dysfunction. By day 28, no differences are observable in proportion achieving weight gain >5 g/kg/day (87%, 92%, 86%; p > 0.05), mortality (16%, 30%, 17%; p > 0.05), or edema resolution (83%, 54%, 91%; p > 0.05) among CpF, InF, and ConF. Decreased fecal bacterial richness from day 1 (abundance-based coverage estimator [ACE] 53.2) to day 7 (ACE 40.8) is observed only in ConF (p = 0.025). Bifidobacterium relative abundance increases from day 7 (5.8% ± 8.6%) to day 28 (10.9% ± 8.7%) in CpF (corrected p = 1.000). Legume-enriched feeds support aspects of gut function and the microbiome. Trial registration PACTR201805003381361.

Effects of microplastics exposure on ingestion, fecundity, development, and dimethylsulfide production in Tigriopus japonicus (Harpacticoida, copepod).

The effects of microplastics pollution on the marine ecosystem have aroused attention. Copepod grazing stimulates dimethylsulfide (DMS) release from dimethylsulfoniopropionate (DMSP) in phytoplankton, but the effect of microplastics exposure on DMS and DMSP production during copepod feeding has not yet been revealed. Here, we investigated the effects of polyethylene (PE) and polyamide-nylon 6 (PA 6) microplastics on ecotoxicity and DMS/DMSP production in the copepod Tigriopus japonicus. The microplastics had detrimental effects on feeding, egestion, reproduction, survival, and DMS and DMSP production in T. japonicus and presented significant dose-response relationships. The 24 h-EC50 for ingestion rates (IRs) of female T. japonicus exposed to PE and PA 6 were 57.6 and 58.9 mg L-1, respectively. In comparison, the body size of the copepods was not significantly affected by the microplastics during one generation of culture. Ingesting fluorescently labeled microplastics confirmed that microplastics were ingested by T. japonicus and adhered to the organs of the body surface. T. japonicus grazing promoted DMS release originating from degradation of DMSP in algal cells. Grazing-activated DMS production decreased because of reduced IR in the presence of microplastics. These results provide new insight into the biogeochemical cycle of sulfur during feeding in copepods exposed to microplastics.