Potential of novel dextran oligosaccharides as prebiotics for obesity management through in vitro experimentation

The energy-salvaging capacity of the gut microbiota from dietary ingredients has been proposed as a contributing factor for the development of obesity. This knowledge generated interest in the use of non-digestible dietary ingredients such as prebiotics to manipulate host energy homeostasis. In the present study, the in vitro response of obese human faecal microbiota to novel oligosaccharides was investigated. Dextrans of various molecular weights and degrees of branching were fermented with the faecal microbiota of healthy obese adults in pH-controlled batch cultures. Changes in bacterial populations were monitored using fluorescent in situ hybridisation and SCFA concentrations were analysed by HPLC. The rate of gas production and total volume of gas produced were also determined. In general, the novel dextrans and inulin increased the counts of bifidobacteria. Some of the dextrans were able to alter the composition of the obese human microbiota by increasing the counts of Bacteroides–Prevotella and decreasing those of Faecalibacterium prausnitzii and Ruminococcus bromii/R. flavefaciens. Considerable increases in SCFA concentrations were observed in response to all substrates. Gas production rates were similar during the fermentation of all dextrans, but significantly lower than those during the fermentation of inulin. Lower total gas production and shorter time to attain maximal gas production were observed during the fermentation of the linear 1 kDa dextran than during the fermentation of the other dextrans. The efficacy of bifidobacteria to ferment dextrans relied on the molecular weight and not on the degree of branching. In conclusion, there are no differences in the profiles between the obese and lean human faecal fermentations of dextrans

The prebiotic effect of α-1,2 branched, low molecular weight dextran in the batch and continuous faecal fermentation system

The aim of this study was to establish the effect of smaller molecular weight (0.5 and 1.0 kDa) on prebiotic efficacy and its putative sustainability in the human gut. The prebiotic effect of α-1,2 branched, 0.5 and 1 kDa dextrans were evaluated in faecal batch fermentations as compared with inulin. Both dextrans induce similar selectivity towards Bifidobacterium sp., Lactobacillus/Enterococcus and Bacteroides/Prevotella, and producing similar concentrations of short chain fatty acids. However, the 0.5 kDa dextran was fermented faster than the 1 kDa dextran, where both produced lower amount of gas than inulin. The fermentation of 1 kDa dextran was further investigated in continuous gut models. The dextran increased Bifidobacterium and Roseburia sp. populations in the final vessel, while decreasing Clostridium histolyticum and Faecalibacterium prausnitzii. Overall, the α-1,2 branched, 1 kDa dextran induced selective effect on the gut microbiota and stimulated short chain fatty acids, indicating prebiotic sustainability in distal regions of the gut

Diagnostic accuracy of a three-gene Mycobacterium tuberculosis host response cartridge using fingerstick blood for childhood tuberculosis: a multicentre prospective study in low-income and middle-income countries

BACKGROUND: Childhood tuberculosis remains a major cause of morbidity and mortality in part due to missed diagnosis. Diagnostic methods with enhanced sensitivity using easy-to-obtain specimens are needed. We aimed to assess the diagnostic accuracy of the Cepheid Mycobacterium tuberculosis Host Response prototype cartridge (MTB-HR), a candidate test measuring a three-gene transcriptomic signature from fingerstick blood, in children with presumptive tuberculosis disease. METHODS: RaPaed-TB was a prospective diagnostic accuracy study conducted at four sites in African countries (Malawi, Mozambique, South Africa, and Tanzania) and one site in India. Children younger than 15 years with presumptive pulmonary or extrapulmonary tuberculosis were enrolled between Jan 21, 2019, and June 30, 2021. MTB-HR was performed at baseline and at 1 month in all children and was repeated at 3 months and 6 months in children on tuberculosis treatment. Accuracy was compared with tuberculosis status based on standardised microbiological, radiological, and clinical data. FINDINGS: 5313 potentially eligible children were screened, of whom 975 were eligible. 784 children had MTB-HR test results, of whom 639 had a diagnostic classification and were included in the analysis. MTB-HR differentiated children with culture-confirmed tuberculosis from those with unlikely tuberculosis with a sensitivity of 59·8% (95% CI 50·8–68·4). Using any microbiological confirmation (culture, Xpert MTB/RIF Ultra, or both), sensitivity was 41·6% (34·7–48·7), and using a composite clinical reference standard, sensitivity was 29·6% (25·4–34·2). Specificity for all three reference standards was 90·3% (95% CI 85·5–94·0). Performance was similar in different age groups and by malnutrition status. Among children living with HIV, accuracy against the strict reference standard tended to be lower (sensitivity 50·0%, 15·7–84·3) compared with those without HIV (61·0%, 51·6–69·9), although the difference did not reach statistical significance. Combining baseline MTB-HR result with one Ultra result identified 71·2% of children with microbiologically confirmed tuberculosis. INTERPRETATION: MTB-HR showed promising diagnostic accuracy for culture-confirmed tuberculosis in this large, geographically diverse, paediatric cohort and hard-to-diagnose subgroups. FUNDING: European and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung; German Center for Infection Research (DZIF)

Effects of sago starch on body weight, food intake, caecum short chain fatty acids, adipose tissue, and hepatic lipid content of fat-induced Sprague Dawley rats

Sago starch which naturally contains high amount of resistant starch, comes to the attention due to its ability to confer health benefits as functional food i.e., prebiotic. The present work aimed to investigate the effects of sago starch consumption on body weight, satiation, caecum short chain fatty acids body, and hepatic lipid content on diet-induced obese rats for obesity management. A total of 36 male Sprague Dawley rats were fat-induced and divided into the obesity-prone and obesity-resistant groups. Eight percent and sixteen percent resistant starch from sago and Hi-maize260 were incorporated into the standardised feed formulation. Food intake was weighed throughout the intervention period. The caecum sample was subjected to short chain fatty acids analysis using HPLC. Hepatic lipid content was measured using the Folch method. Both dosages of sago starch (8 and 16% SRS) promoted body weight loss with a reduction of food intake, which suggested satiety. No significant differences was observed in the production of lactate, acetate, propionate, and butyrate from the caecum sample. Both dosages of sago starch (8 and 16% SRS) also showed lower hepatic lipid content and visceral adipose tissue than the baseline and control groups. However, 8% sago starch showed the lowest hepatic lipid content in obesity-prone and obesity-resistant groups. Overall results demonstrated that sago starch has the potential as an obesity and overweightness control regime as it promotes satiety, lowers visceral adipose tissue, and reduces hepatic lipid content. Consumers should consider adding sago starch in their daily meals

Probing ultrafast ππ*/nπ* internal conversion in organic chromophores via K-edge resonant absorption

Many photoinduced processes including photosynthesis and human vision happen in organic molecules and involve coupled femtosecond dynamics of nuclei and electrons. Organic molecules with heteroatoms often possess an important excited-state relaxation channel from an optically allowed ππ* to a dark nπ* state. The ππ*/nπ* internal conversion is difficult to investigate, as most spectroscopic methods are not exclusively sensitive to changes in the excited-state electronic structure. Here, we report achieving the required sensitivity by exploiting the element and site specificity of near-edge soft X-ray absorption spectroscopy. As a hole forms in the n orbital during ππ*/nπ* internal conversion, the absorption spectrum at the heteroatom K-edge exhibits an additional resonance. We demonstrate the concept using the nucleobase thymine at the oxygen K-edge, and unambiguously show that ππ*/nπ* internal conversion takes place within (60 ± 30) fs. High-level-coupled cluster calculations confirm the method’s impressive electronic structure sensitivity for excited-state investigations