Rates of production and utilisation of lactate by microbial communities from the human colon

13 páginas, 7 tablas, 3 figuras.Lactate metabolism was studied in mixed bacterial communities using single-stage continuous flow fermentors inoculated with faecal slurries from four different volunteers and run for 6 days at pH 5.5 and 6.0, using carbohydrates, mainly starch, as substrates. A continuous infusion of [U-13C]starch and l-[3-13C]lactate was performed on day 5 and a bolus injection of l-[3-13C]lactate plus dl-lactate on day 6. Short-chain fatty acids and lactate concentrations plus enrichments and numbers of lactate-producing and -utilizing bacteria on day 5 were measured. Faecal samples were also collected weekly over a 3-month period to inoculate 24-h batch culture incubation at pH 5.9 and 6.5 with carbohydrates alone or with 35 mmol L-1 lactate. In the fermentors, the potential lactate disposal rates were more than double the formation rates, and lactate concentrations usually remained below detection. Lactate formation was greater (P < 0.05) at the lower pH, with a similar tendency for utilization. Up to 20% of butyrate production was derived from lactate. In batch cultures, lactate was also efficiently used at both pH values, especially at 6.5, although volunteer and temporal variability existed. Under healthy gut environmental conditions, bacterial lactate disposal seems to exceed production markedly.The Rowett Research Institute and Biomathematics and Statistics Scotland are supported by the Scottish Executive Environment and Rural Affairs Department. A. Belenguer received financial support from Spanish Ministry of Education and Science

Higher total faecal short chain fatty concentrations correlate with increasing proportions of butyrate and decreasing proportions of branched chain fatty acids across multiple human studies

The Rowett Institute (University of Aberdeen) receives financial support from the Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS). Studies 779 and 780 were supported by a grant from the World Cancer Research Fund.Peer reviewedPublisher PD

Higher total faecal short-chain fatty acid concentrations correlate with increasing proportions of butyrate and decreasing proportions of branched-chain fatty acids across multiple human studies

Metabolites produced by microbial fermentation in the human intestine, especially short-chain fatty acids (SCFAs), are known to play important roles in colonic and systemic health. Our aim here was to advance our understanding of how and why their concentrations and proportions vary between individuals. We have analysed faecal concentrations of microbial fermentation acids from 10 human volunteer studies, involving 163 subjects, conducted at the Rowett Institute, Aberdeen, UK over a 7-year period. In baseline samples, the % butyrate was significantly higher, whilst % iso-butyrate and % iso-valerate were significantly lower, with increasing total SCFA concentration. The decreasing proportions of iso-butyrate and iso-valerate, derived from amino acid fermentation, suggest that fibre intake was mainly responsible for increased SCFA concentrations. We propose that the increase in % butyrate among faecal SCFA is largely driven by a decrease in colonic pH resulting from higher SCFA concentrations. Consistent with this, both total SCFA and % butyrate increased significantly with decreasing pH across five studies for which faecal pH measurements were available. Colonic pH influences butyrate production through altering the stoichiometry of butyrate formation by butyrate-producing species, resulting in increased acetate uptake and butyrate formation, and facilitating increased relative abundance of butyrate-producing species (notably Roseburia and Eubacterium rectale).The Rowett Institute (University of Aberdeen) receives financial support from the Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS). Studies 779 and 780 were supported by a grant from the World Cancer Research Fund.Peer reviewe

Determination of the prebiotic activity of wheat arabinogalactan peptide (AGP) using batch culture fermentation

Purpose To test the prebiotic activity of wheat arabinogalactan-peptide (AGP), which is a soluble dietary fibre composed of arabinogalactan polysaccharide linked to a 15-residue peptide, which accounts for up to 0.4% of the dry weight of wheat flour. Methods The prebiotic activity of AGP prepared from white wheat flour was tested using in-vitro fermentation by colonic bacteria in automated pH controlled anaerobic stirred batch cultures and compared to fructooligosaccharide (FOS) and wheat flour arabinoxylan (AX). Bacterial populations were measured using fluorescence in-situ hybridisation (flow-FISH) and short-chain fatty acid (SCFA) concentrations were measured using HPLC. Results Fermentation of AGP resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate after 24 h of fermentation. Conclusions These results were comparable to those obtained with AX and confirm the prebiotic potential of AGP. Furthermore, fermentation of a mixture of AGP and AX was faster compared to the single substrates and more similar to FOS, indicating that combinations of fermentable carbohydrates with different structures are potentially more effective as prebiotics than single substrates

Resistant Starch: Promise for Improving Human Health

Ongoing research to develop digestion-resistant starch for human health promotion integrates the disciplines of starch chemistry, agronomy, analytical chemistry, food science, nutrition, pathology, and microbiology. The objectives of this research include identifying components of starch structure that confer digestion resistance, developing novel plants and starches, and modifying foods to incorporate these starches. Furthermore, recent and ongoing studies address the impact of digestion-resistant starches on the prevention and control of chronic human diseases, including diabetes, colon cancer, and obesity. This review provides a transdisciplinary overview of this field, including a description of types of resistant starches; factors in plants that affect digestion resistance; methods for starch analysis; challenges in developing food products with resistant starches; mammalian intestinal and gut bacterial metabolism; potential effects on gut microbiota; and impacts and mechanisms for the prevention and control of colon cancer, diabetes, and obesity. Although this has been an active area of research and considerable progress has been made, many questions regarding how to best use digestion-resistant starches in human diets for disease prevention must be answered before the full potential of resistant starches can be realized

Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.

Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.RCUK Cancer Research UK ERC H2020 Wellcome Trus

Gut microbiota functions: metabolism of nutrients and other food components

The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays

“Es fundamental que la información que se transmita sea confiable”

El flamante Doctor Honoris Causa de la UNLP, Emilio Luque Fadón, de la Universidad Autónoma de Barcelona, fue uno de los conferencistas de CACIC 2017. Durante su estadía por la ciudad de La Plata, el español habló acerca de las nuevas tecnologías, su tolerancia a los fallos y el consumo energético.Facultad de Informátic

Quantitative analysis of Microbial metabolism in the human large intestine

Microbial metabolism in the human colon impacts on health and disease. Production of intermediate metabolites and end-products depends largely on the supply of dietary carbohydrates, including prebiotics (fructooligosaccharides) and functional foods (resistant starch), that resist small intestinal digestion. Colonic bacteria ferment these substrates to a wide range of products, predominantly short-chain fatty acids, including metabolites that can be either deleterious (e.g. D-lactate, sulphides) or beneficial (e.g. butyrate) to gut health. Lactate accumulation in the colon has been associated with gastrointestinal disturbance, for example in severe ulcerative colitis, whereas in the healthy state lactate is efficiently utilised by gut bacteria. Understanding the interaction between microbial metabolism and diet-derived nutrient supply is crucial for maintaining a healthy metabolic balance in the colon. Prediction of such nutritional responses can be achieved by integrating in mathematical models information from stable isotope studies, that quantify metabolite flows, and molecular techniques, that accurately determine changes in microbial composition diversity. From such approaches, better nutritional advice can be provided in order to improve gut health. Furthermore, such understanding can be used to manipulate and improve the action of prebiotics and probiotics. © 2008 Bentham Science Publishers Ltd.Peer Reviewe