Gut microbiota, its evolutive dynamics and influence on host through its protective, trophic and metabolic actions, has a key role in health and opens unique opportunities for the identification of ...new markers of the physiopathological state of each individual. Alterations in gut microbiota composition have been associated with plenty disorders. Of interest, the vast number of studies demonstrates the role of microbiota in obesity, a serious public health problem that has reached epidemic proportions in many developed and middle-income countries. The economic and health costs of this condition and its comorbidities such as fatty liver, insulin resistance/diabetes, or cardiovascular events are considerable. Therefore, every strategy designed to reduce obesity would imply important savings. Targeting microbiota, in order to restore/modulate the microbiota composition with antibiotics, probiotics, prebiotics, or even fecal transplants, is considered as a promising strategy for the development of new solutions for the treatment of obesity. However, there is still lot to do in this field in order to identify the exact composition of microbiota in “health” and the specific mechanisms that regulate the host-microbiotal crosstalk. In addition, it is important to note that changes not only in the gut microbiota profile (abundance) but also in its metabolism and functions need to be taken into account in the context of contribution in the physiopathology of obesity and related disorders.
Resveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this ...context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several
Lactobacillus
,
Clostridium
, and
Bacteroides
species belonging to
Firmicutes
and
Bacteroidetes
. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications.
Clinical decompensation of cirrhosis is associated with poor prognosis. Clinically significant portal hypertension (CSPH), defined by a hepatic venous pressure gradient (HVPG) ≥10 mm Hg, is the ...strongest predictor of decompensation. This study aimed at assessing whether lowering HVPG with β blockers could decrease the risk of decompensation or death in compensated cirrhosis with CSPH.
This study on β blockers to prevent decompensation of cirrhosis with portal hypertension (PREDESCI) was an investigator-initiated, double-blind, randomised controlled trial done in eight hospitals in Spain. We enrolled patients with compensated cirrhosis and CSPH without high-risk varices. All participants had HVPG measurements with assessment of acute HVPG-response to intravenous propranolol. Responders (HVPG-decrease ≥10%) were randomly assigned to propranolol (up to 160 mg twice a day) versus placebo and non-responders to carvedilol (≤25 mg/day) versus placebo. Doses were individually determined during an open-label titration period after which randomisation was done with 1:1 allocation by a centralised web-based system. The primary endpoint was incidence of cirrhosis decompensation (defined as development of ascites, bleeding, or overt encephalopathy) or death. Since death in compensated cirrhosis is usually unrelated to the liver, an intention-to-treat analysis considering deaths unrelated to the liver as competing events was done. This study is registered with ClinicalTrials.gov, number NCT01059396. The trial is now completed.
Between Jan 18, 2010, and July 31, 2013, 631 patients were evaluated and 201 were randomly assigned. 101 patients received placebo and 100 received active treatment (67 propranolol and 33 carvedilol). The primary endpoint occurred in 16 (16%) of 100 patients in the β blockers group versus 27 (27%) of 101 in the placebo group (hazard ratio HR 0·51, 95% CI 0·26–0·97, p=0·041). The difference was due to a reduced incidence of ascites (HR 0·42, 95% CI 0·19–0·92, p=0·03). The overall incidence of adverse events was similar in both groups. Six patients (four in the β blockers group) had severe adverse events.
Long-term treatment with β blockers could increase decompensation-free survival in patients with compensated cirrhosis and CSPH, mainly by reducing the incidence of ascites.
Spanish Ministries of Health and Economy.
Introduction: Increased bacterial translocation and alterations to gut microbiota composition have been described in HIV infection and contribute to immune activation and inflammation. These effects ...persist despite combined antiretroviral therapy (cART). However, the contribution of different cART combinations has not yet been investigated. The aim of this study was to analyse the long‐term effects of different combinations of cART on bacterial translocation and gut microbiota composition in HIV‐infected patients.
Methods: We carried out a cross‐sectional study of 45 HIV‐infected patients on cART, classified as nucleoside reverse transcriptase inhibitors (NRTIs)+ protease inhibitors (PIs) (n = 15), NRTIs+ non‐nucleoside reverse transcriptase inhibitors (NNRTIs) (n = 22), and NRTIs+ integrase strand transfer inhibitors (INSTIs) (n = 8). Untreated HIV‐infected patients (n = 5) and non‐infected volunteers (n = 21) were also included. Soluble markers of bacterial translocation and inflammation were measured and gut microbiota composition was analysed using 16S rDNA pyrosequencing (Illumina MiSeq).
Results: The NRTIs+INSTIs regimen was associated with levels of systemic inflammation that were similar to uninfected controls. The reduction in faecal bacterial diversity induced by HIV infection was also restored by this regimen. HIV infection was more closely related to changes in lower taxonomic units and diversity rather than at the phylum level. The NRTIs+PIs regimen showed the highest reduction in bacterial species, whereas NRTIs+INSTIs induced a minor loss of bacterial species and a significant increase in others.
Conclusions: Our study demonstrated that INSTI‐based ART was associated with levels of systemic inflammation and microbial diversity similar to that of uninfected controls. The role of INSTIs other than raltegravir needs to be further investigated. Patients on the NRTIs+PIs regimen presented the highest reduction in bacterial species compared with other antiretrovirals and naive patients. Thus, different cART regimens are associated with diverse profiles in gut microbiota composition. Longitudinal and functional studies are needed to better understand these findings.
Background and ImportanceThe FDA Adverse Reporting System (FAERS) is a tool to voluntary report adverse events (AE), These data can be downloaded and used to apply ‘Machine learning’(ML) techniques. ...The bibliography is limited, although it has already been the subject of a systematic review (Kim et al, 2022). FAERS data set could be useful to elaborate potential predictive modelling.Aim and ObjectivesTo test a tool of ML to develop a potential predictive model of AE caused by immune checkpoint inhibitors (ICI), using FAERS data set.To contrast and explain the ML results with a reference model (RM), obtained through conventional processing data (spreadsheet).Material and MethodsAll FAERS records from 2022 were downloaded, selecting those of the group ICIs group notified as ‘main suspected drug’ (inclusion criteria). Collected variables from FAERS data set were:AE, age, drug and sex. The ML decision tree classification algorithm J48 implemented in the Weka application (version 3.8.6) was used to elaborate the ML model. The RM was built using a spreadsheet to tabulate and analyse the data (pivot tables and descriptive statistics).Results1,702,222 notifications were downloaded and 86,053 records were selected according to inclusion criteria. The J48 algorithm applied to a subset including ‘adverse effect’, ‘sex’ and ‘drug’, allowed us to estimate, for each AE the most likely responsible ICI drug. The metrics of the ML model obtained were satisfactory and compatible with the RM analysis. The J48 algorithm produced a complex tree (to be expected given the large number of AE). The application of J48 on another subset that includes ‘adverse effect’, ‘age’ and ‘drug’, had a lower predictive capacity, due to the lower consistency of the data (age is only recorded as younger or older than 65 years) and that there is a higher proportion of missing values. The RM allows the results obtained with ML to be easily explained and understood.Conclusion and RelevanceThe results of the J48 algorithm were useful for the association between AE, sex and drug. Despite the inherent limitations of voluntary AE reporting, this study will serve as a starting point for applying ML techniques in any other group, using FAERS data.References and/or Acknowledgements1. Kim, et al. 2022. 10.1097/MD.0000000000029387Conflict of InterestNo conflict of interest.
The link between intestinal inflammation, microbiota, and colorectal cancer is intriguing and the potential underlying mechanisms remain unknown. Here we evaluate the influence of adrenomedullin (AM) ...in microbiota composition and its impact on colitis with an inducible knockout (KO) mouse model for AM. Microbiota composition was analyzed in KO and wild type (WT) mice by massive sequencing. Colitis was induced in mice by administration of azoxymethane (AOM) followed by dextran sulfate sodium (DSS) in the drinking water. Colitis was evaluated using a clinical symptoms index, histopathological analyses, and qRT-PCR. Abrogation of the
gene in the whole body was confirmed by PCR and qRT-PCR. KO mice exhibit significant changes in colonic microbiota: higher proportion of δ
class; of
order; and of other families and genera was observed in KO feces. Meanwhile these mice had a lower proportion of beneficial bacteria, such as
and
. TLR4 gene expression was higher (
< 0.05) in KO animals. AM deficient mice treated with DSS exhibited a significantly worse colitis with profound weight loss, severe diarrhea, rectal bleeding, colonic inflammation, edema, infiltration, crypt destruction, and higher levels of pro-inflammatory cytokines. No changes were observed in the expression levels of adhesion molecules. In conclusion, we have shown that lack of AM leads to changes in gut microbiota population and in a worsening of colitis conditions, suggesting that endogenous AM is a protective mediator in this pathology.
Irritable bowel syndrome (IBS) includes diarrhea-predominant (IBS-D) and constipation-predominant (IBS-C) subtypes. We combined breath testing and stool microbiome sequencing to identify potential ...microbial drivers of IBS subtypes.
IBS-C and IBS-D subjects from 2 randomized controlled trials (NCT03763175 and NCT04557215) were included. Baseline breath carbon dioxide, hydrogen (H 2 ), methane (CH 4 ), and hydrogen sulfide (H 2 S) levels were measured by gas chromatography, and baseline stool microbiome composition was analyzed by 16S rRNA sequencing. Microbial metabolic pathways were analyzed using Kyoto Encyclopedia of Genes and Genomes collection databases.
IBS-C subjects had higher breath CH 4 that correlated with higher gut microbial diversity and higher relative abundance (RA) of stool methanogens, predominantly Methanobrevibacter , as well as higher absolute abundance of Methanobrevibacter smithii in stool. IBS-D subjects had higher breath H 2 that correlated with lower microbial diversity and higher breath H 2 S that correlated with higher RA of H 2 S-producing bacteria, including Fusobacterium and Desulfovibrio spp. The predominant H 2 producers were different in these distinct microtypes, with higher RA of Ruminococcaceae and Christensenellaceae in IBS-C/CH 4 + (which correlated with Methanobacteriaceae RA) and higher Enterobacteriaceae RA in IBS-D. Finally, microbial metabolic pathway analysis revealed enrichment of Kyoto Encyclopedia of Genes and Genomes modules associated with methanogenesis and biosynthesis of methanogenesis cofactor F420 in IBS-C/CH 4 + subjects, whereas modules associated with H 2 S production, including sulfate reduction pathways, were enriched in IBS-D.
Our findings identify distinct gut microtypes linked to breath gas patterns in IBS-C and IBS-D subjects, driven by methanogens such as M. smithii and H 2 S producers such as Fusobacterium and Desulfovibrio spp, respectively.
Spray drying is a well-known operation to formulate food powders. Usually, the dryer performance is evaluated through trial and error given the complexity of transport phenomena. Regarding the ...microencapsulation of functional chia oil by spray drying, the main contribution of this study was to compare the accuracy of fundamental models for predicting the values of process variables (drying-air outlet temperature, Toutlet and feed flow rate, Vfeed) and powder properties (size, d32 and moisture content, H), under a wide range of drying conditions at laboratory (Büchi B-290) and pilot scales (Niro Production Minor). First, the coarse-scale approach modeled the dryer's chamber as a well-mixed reactor. The experimental values for Toutlet were: 72–109 °C (laboratory scale) and 75, 90 °C (pilot scale); moreover, the experimental Vfeed values were in the following ranges: 2.8 and 5.6 mL.min−1 (laboratory scale) and 59–197 mL.min−1 (pilot scale). With the coarse-scale approach, absolute average deviations (AAD) below 7% between experimental and calculated values were observed for Toutlet and Vfeed. However, large prediction errors (>10%) were observed for H, for which the experimental values were in the range of 2.4–4.5% for both scales. On the contrary, the finer-scale approach consisted of a plug-flow model, with incorporated drying kinetics and spray droplet sizes. This model could accurately predict Toutlet, H and d32, with AAD values below 10%. Both simulation and experiments are useful tools not only for spray drying optimization, but also for improving the oxidative stability of microencapsulated oils by target-oriented design.
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•A spray-drying process for the encapsulation of chia oil was modeled.•Coarse and finer-scale models were applied for laboratory and pilot-scale dryers.•Air outlet temperature and feed rate were accurately predicted by the coarse-scale model.•Better predictions for moisture content were obtained with the finer-scale model.•The finer-scale model can be used for a rapid estimation of spray-dryers' performance.
Background
We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (H
2
S)-producing
Fusobacterium
and
...Desulfovibrio
species, and constipation-predominant IBS (IBS-C) subjects have higher RA of methanogen
Methanobrevibacter smithii
.
Aims
In this study, we investigate the effects of increased methanogens or H
2
S producers on stool phenotypes in rat models.
Methods
Adult Sprague–Dawley rats were fed high-fat diet (HFD) for 60 days to increase
M. smithii
levels, then gavaged for 10 days with water (controls) or methanogenesis inhibitors. To increase H
2
S producers, rats were gavaged with
F. varium
or
D. piger
. Stool consistency (stool wet weight (SWW)) and gas production were measured. 16S rRNA gene sequencing was performed on stool samples.
Results
In HFD diet-fed rats (
N
= 30), stool
M. smithii
levels were increased (
P
< 0.001) after 52 days, correlating with significantly decreased SWW (
P
< 0.0001) at 59 days (
R
= − 0.38,
P
= 0.037). Small bowel
M. smithii
levels decreased significantly in lovastatin lactone-treated rats (
P
< 0.0006), and SWW increased (normalized) in lovastatin hydroxyacid-treated rats (
P
= 0.0246), vs. controls (
N
= 10/group). SWW increased significantly in
D. piger
-gavaged rats (
N
= 16) on day 10 (
P
< 0.0001), and in
F. varium
-gavaged rats (
N
= 16) at all timepoints, vs. controls, with increased stool H
2
S production. 16S sequencing revealed stool microbiota alterations in rats gavaged with H
2
S producers, with higher relative abundance (RA) of other H
2
S producers, particularly Lachnospiraceae and
Bilophila
in
F. varium
-gavaged rats, and
Sutterella
in
D. piger
-gavaged rats.
Conclusions
These findings suggest that increased
M. smithii
levels result in a constipation-like phenotype in a rat model that is partly reversible with methanogenesis inhibitors, whereas gavage with H
2
S producers
D. piger
or
F. varium
results in increased colonization with other H
2
S producers and diarrhea-like phenotypes. This supports roles for the increased RA of methanogens and H
2
S producers identified in IBS-C and IBS-D subjects, respectively, in contributing to stool phenotypes.
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