Summary
Background
Butyrate, propionate and acetate are short chain fatty acids (SCFA), important for maintaining a healthy colon and are considered as protective in colorectal carcinogenesis. ...However, they may also regulate immune responses and the composition of the intestinal microbiota. Consequently, their importance in a variety of chronic inflammatory diseases is emerging.
Aims
To review the physiology and metabolism of SCFA in humans, cellular and molecular mechanisms by which SCFA may act in health and disease, and approaches for therapeutic delivery of SCFA.
Methods
A PubMed literature search was conducted for clinical and pre‐clinical studies using search terms: ‘dietary fibre’, short‐chain fatty acids’, ‘acetate’, ‘propionate’, ‘butyrate’, ‘inflammation’, ‘immune’, ‘gastrointestinal’, ‘metabolism’.
Results
A wide range of pre‐clinical evidence supports roles for SCFA as modulators of not only colonic function, but also multiple inflammatory and metabolic processes. SCFA are implicated in many autoimmune, allergic and metabolic diseases. However, translating effects of SCFA from animal studies to human disease is limited by physiological and dietary differences and by the challenge of delivering sufficient amounts of SCFA to the target sites that include the colon and the systemic circulation. Development of novel targeted approaches for colonic delivery, combined with postbiotic supplementation, may represent desirable strategies to achieve adequate targeted SCFA delivery.
Conclusions
There is a large array of potential disease‐modulating effects of SCFA. Adequate targeted delivery to the sites of action is the main limitation of such application. The ongoing development and evaluation of novel delivery techniques offer potential for translating promise to therapeutic benefit.
Summary
Background
Beneficial effects of carbohydrate fermentation on gastrointestinal health are well established. Conversely, protein fermentation generates harmful metabolites but their relevance ...to gastrointestinal health is poorly understood.
Aim
To review the effects of increased protein fermentation on biomarkers of colonic health, factors influencing fermentative activity and potential for dietary modulation to minimise detrimental effects.
Methods
A literature search was performed in PubMed, Medline, EMBASE and Google scholar for clinical and pre‐clinical studies using search terms – ‘dietary protein’, ‘fermentation’, ‘putrefaction’, ‘phenols’, ‘sulphide’, ‘branched‐chain fatty acid’, ‘carbohydrate fermentation’, ‘gastrointestinal’.
Results
High protein, reduced carbohydrate diets alter the colonic microbiome, favouring a potentially pathogenic and pro‐inflammatory microbiota profile, decreased short‐chain fatty acid production and increased ammonia, phenols and hydrogen sulphide concentrations. These metabolites largely compromise the colonic epithelium structure, causing mucosal inflammation but may also directly modulate the enteric nervous system and intestinal motility. Increased protein fermentation as a result of a high‐protein intake can be attenuated by addition of oligosaccharides, resistant starch and nonstarch polysaccharides and a reduction in total protein or specifically, aromatic and sulphur‐containing amino acids. These factors may have clinical importance as novel therapeutic approaches to problems, in which protein fermentation may be implicated, such as malodorous flatus, irritable bowel syndrome, ulcerative colitis and prevention of colorectal cancer.
Conclusions
The direct clinical relevance of excessive protein fermentation in the pathogenesis of irritable bowel syndrome, malodorous flatus and ulcerative colitis are underexplored. Manipulating dietary carbohydrate and protein intake have potential therapeutic applications in such settings and warrant further clinical studies.
Chronic liver diseases (CLDs), due to chronic hepatitis C; hepatitis B; nonalcoholic fatty liver diseases (NAFLD); and alcoholic liver disease, are a leading cause of morbidity and mortality ...globally. Early identification of patients with cirrhosis at high risk of progression to liver-related complications may facilitate timely care and improve outcomes. With risks and misclassification associated with invasive tests, such as liver biopsy, noninvasive imaging modalities for liver fibrosis assessment have gained popularity. Therefore, the American Gastroenterological Association prioritized clinical guidelines on the role of elastography in CLDs, focusing on vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE). To inform these clinical guidelines, the current technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for diagnostic accuracy studies. This technical review addresses focused questions related to: (1) comparative diagnostic performance of VCTE and MRE relative to nonproprietary, serum-based fibrosis markers for detection of cirrhosis in patients with hepatitis C virus (HCV), hepatitis B virus (HBV), NAFLD, and alcoholic liver diseases; (2) performance of specific VCTE-defined liver stiffness cutoffs as a test replacement strategy (to replace liver biopsy) in making key decisions in the management of patients with CLDs; and (3) performance of specific VCTE-defined liver stiffness cutoffs as a triage test to identify patients with low likelihood of harboring high-risk esophageal varices (EVs) or having clinically significant portal hypertension (for presurgical risk stratification). This technical review does not address performance of other noninvasive modalities for assessing fibrosis (eg, acoustic radiation force pulse imaging or shear wave elastography) or steatosis (controlled attenuation parameter or magnetic resonance imaging−estimated proton density fat fraction).
Seismology records the presence of various heterogeneities throughout the lower mantle1,2, but the origins of these signals- whether thermal or chemical-remain uncertain, and therefore much of the ...information that they hold about the nature of the deep Earth is obscured. Accurate interpretation of observed seismic velocities requires knowledge of the seismic properties of all of Earth's possible mineral components. Calcium silicate (CaSiO3) perovskite is believed to be the third most abundant mineral throughout the lower mantle. Here we simultaneously measure the crystal structure and the shear-wave and compressional-wave velocities of samples of CaSiO3 perovskite, and provide direct constraints on the adiabatic bulk and shear moduli of this material. We observe that incorporation of titanium into CaSiO3 perovskite stabilizes the tetragonal structure at higher temperatures, and that the material's shear modulus is substantially lower than is predicted by computations3-5 or thermodynamic datasets6. When combined with literature data and extrapolated, our results suggest that subducted oceanic crust will be visible as low-seismic-velocity anomalies throughout the lower mantle. In particular, we show that large low-shear-velocity provinces (LLSVPs) are consistent with moderate enrichment of recycled oceanic crust, and mid-mantle discontinuities can be explained by a tetragonal-cubic phase transition in Ti-bearing CaSiO3 perovskite.
The current standard of care for the treatment of hepatitis C virus (HCV) consists of interferon-free direct-acting antiviral (DAA) regimens, including combinations of DAAs and fixed-dose combination ...pills. DAAs for HCV are likely to be heralded as one of medicine's greatest advancements. Viral eradication rates are pushing 100% for many HCV-infected populations, including patients with HIV HCV coinfection, decompensated cirrhosis, liver and kidney transplants, and end-stage liver disease. We highlight the greatest successes of combination DAA therapies, discuss the ongoing challenges, and identify the remaining patient subgroups with unmet medical needs.
Progression of nonalcoholic steatohepatitis (NASH) is incompletely characterized. We analyzed data on longitudinal changes in liver histology, hepatic venous pressure gradient (HVPG), and serum ...markers of fibrosis in 475 patients with NASH with bridging fibrosis (F3) or compensated cirrhosis (F4) enrolled in two phase 2b, placebo‐controlled trials of simtuzumab. The trials were terminated after 96 weeks because of lack of efficacy, so data from treatment groups were combined. Liver biopsies and HVPG measurements (only for patients with F4 fibrosis) were collected at screening and at weeks 48 and 96. Patients were assessed for Ishak fibrosis stage, hepatic collagen content and alpha‐smooth muscle actin (by morphometry), NAFLD Activity Score (NAS), and serum markers of fibrosis. Associations with progression to cirrhosis (in patients with F3 fibrosis) and liver‐related clinical events (in patients with F4 fibrosis) were determined. Progression to cirrhosis occurred in 22% (48/217) of F3 patients, and liver‐related clinical events occurred in 19% (50/258) of patients with cirrhosis. Factors significantly associated with progression to cirrhosis included higher baseline values of and greater increases in hepatic collagen content, level of alpha‐smooth muscle actin, and Enhanced Liver Fibrosis score. Similar factors, plus lack of fibrosis stage improvement (hazard ratio, 9.30; 95% confidence interval, 1.28‐67.37), higher HVPG at baseline, and greater increase in HVPG over time, were associated with an increased risk of liver‐related clinical events in patients with cirrhosis. Disease progression was not associated with the NAS at baseline or changes in NAS during treatment after adjustment for fibrosis stage. Conclusion: In patients with advanced fibrosis due to NASH, the primary determinant of clinical disease progression is fibrosis and its change over time.
Summary
Background Functional gut symptoms are induced by inclusion and reduced by dietary restriction of poorly absorbed short‐chain carbohydrates (FODMAPs), but the mechanisms of action remain ...untested.
Aims To determine the effect of dietary FODMAPs on the content of water and fermentable substrates of ileal effluent.
Methods Twelve ileostomates without evidence of small intestinal disease undertook two 4‐day dietary periods, comprising diets differing only in FODMAP content in a randomized, cross‐over, single‐blinded intervention study. Daytime (14 h) ileal effluent was collected on day four of each diet. Patients rated effluent volume and consistency on a 10‐cm visual analogue scale. The FODMAP content of the diet and effluent was measured.
Results Ingested FODMAPs of 32% (range 6–73%) was recovered in the high FODMAP diet effluent. Effluent collection weight increased by a mean of 22% (95% CI, 5–39), water content by 20% (2–38%) and dry weight by 24% (4–43%) with the high compared to low FODMAP diet arm. Output increased by 95 (28–161) mL. Volunteers perceived effluent consistency was thicker (95% CI, 0.6–1.9) with the low FODMAP diet than with the high FODMAP diet (3.5–6.1; P = 0.006).
Conclusions These data support the hypothetical mechanism; FODMAPs increase delivery of water and fermentable substrates to the proximal colon.
In this phase 3 study involving patients with HCV genotype 1, 2, 3, 4, or 6 and decompensated cirrhosis, sofosbuvir–velpatasvir with or without ribavirin for 12 weeks or sofosbuvir–velpatasvir for 24 ...weeks resulted in high rates of sustained virologic response.
The number of patients with decompensated cirrhosis caused by chronic infection with the hepatitis C virus (HCV) is projected to rise in the coming decade.
1
For many years, the only treatment option for such patients was liver transplantation. Recently, however, clinical trials of newly approved direct-acting antiviral agents have shown that it is possible to treat HCV infection safely and effectively in patients with decompensated cirrhosis and that successful treatment is associated with early improvement in liver function.
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The possible long-term benefits of treatment on existing liver disease remain unknown. The only regimen that is currently approved for the . . .
•Two stage alkali pretreatment process was optimized to maximize xylan recovery.•Optimized conditions for 1st stage: 10% w/v NaOH, incubated at 65 °C for 8 h.•Optimized conditions for 2nd stage: ...Hydrothermal treatment (121 °C for 1 h).•Enzymatic hydrolysis of xylan yielded 35 g/100 g pure xylan at optimized conditions.•XOS was rich in xylobiose (71% of XOS) and xylotriose (26%).
In the present work, xylan from arecanut husk was extracted using 2 stage alkaline pretreatment process. In first step, biomass was incubated in alkali at different temperatures (25 °C, 50 °C and 65 °C), alkali concentrations (5%, 10%, 15% and 20% w/v), and incubation periods (8 h, 16 h and 24 h) and evaluated for xylan recovery. It was observed that 40–52% of available xylan could be recovered using 10% alkali when incubated for 8–24 h at 65 °C. Subsequently, the alkali pretreatment operating conditions which provided good xylan recovery were processed further using hydrothermal treatment to extract more xylan. For maximum xylan recovery (>90%), best operating conditions were identified when biomass was treated under hydrothermal treatment (1, 1.5 and 2 h) with varying incubation periods (8, 16, 24 h) and alkali concentrations (5%, 10%) using full factorial design. Incubating arecanut husk with 10% w/v NaOH, at 65 °C for a period of 8 h, followed by hydrothermal treatment at 121 °C for 1 h helped recover >94% xylan. In the next step, enzymatic hydrolysis process was optimized to recover maximum XOS (Optimized condition: 50 °C, pH 4 and 10 U enzyme dose). The hydrolysate comprised of xylobiose: 25.0 ± 1.2 g/100 g xylan (∼71% of XOS), xylotriose: 9.2 ± 0.65 g/100 g xylan (26.2% of XOS) and xylotetrose: 0.9 ± 0.04 g/100 g xylan (2% of XOS). The developed process enables to reduce alkali consumption for high recovery of xylan from biomass with relatively higher lignin content for its valorisation into a potential prebiotic oligosaccharide.
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