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For any enquiries related to the Microbiome and Diet research area, please contact

Fiona Pereira
CSM Research Manager
csm@imperial.ac.uk

+44 (0)20 7594 3197

Probing the host-microbe-diet interface

The gut microbiota refers to the micro-organisms (bacteria, archaea, fungi, protozoa, helminths) and viruses found in the human gastrointestinal tract, while the gut microbiome refers specifically to the DNA and genes associated with the prokaryotes, eukaryotes and viruses that contribute to the gut microbiota. There are as many microbial cells present in the gut as there are human cells in the body, all perform an array of metabolic biotransformations (some of which are not performed by their human hosts), exert an influence on digestive function, and influence the immune system.

Despite some overlap in terms of the bacteria, archaea and viruses present, the exact composition of the gut microbiota varies from individual to individual and in the different regions of the gastrointestinal tract, with the density and complexity of microbial populations increasing from stomach to large intestine. Numerous intrinsic (pH, oxygen availability, bacterial co-operation and antagonism, antimicrobial peptides, transit time, peristalsis, immunoglobulin-containing mucin secretions) and extrinsic (diet, medications) factors affect the composition and functions of the gut microbiota. Age and clinical conditions such as obesity, inflammatory bowel disease, neurodegenerative diseases, liver disease, chronic fatigue syndrome, and type II diabetes also alter the gut microbiota and interactions with its human host.

Diet is clearly relevant in relation to human health in its own right, but it is the interaction between human dietary inputs and the gut microbiome that is currently providing some of the most fascinating insight. Understanding how different diets affect - and are affected by - the human microbiome has the potential to unlock a variety of clinically relevant opportunities, including precise dietary regimens for improved clinical outcomes, and new drug targets.

By integrating clinical, dietary, microbiota/microbiome, gene expression and metabolite data, we identify mechanisms through which all components of the microbiota and their functions influence human health and identify targeted means of manipulating the microbiota to improve human health.


Find out more about our key focus areas:

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Metagenomics

Metagenomic studies that examine the microbiome in great detail have revealed reductions in microbial gene richness and changes in functional capabilities of the faecal microbiome are signatures of obesity, liver disease and type II diabetes, and can be modified by dietary intervention. They have also demonstrated the gut microbiome harbours 150 times more genes than the human genome (3.3 M vs 22,000), significantly increasing the repertoire of functional genes available to humans, and contributing to energy harvesting from food and production of microbiota-associated metabolites that can be detected in human blood, urine, saliva and cerebrospinal fluid. Microbiota-associated metabolites and products such as lipopolysaccharide influence human health at the gastrointestinal, organ and systemic levels, and microbiota-associated metabolites mediate epigenetic programming in multiple host tissues.

Diet and Health

Diet plays a fundamental role in human health and disease. What we eat, how much, and when, all influence central biochemical processes that underpin our health status. Expertise in metabolic phenotyping and compositional analysis by NMR spectroscopy and MS techniques provides CSM researchers with the opportunity to understand the metabolic consequences of different diets, explore rich clinical and population biosample archives to understand dietary behaviors, and augment epidemiological analyses by providing objective measures of dietary exposure, which are notoriously difficult to capture accurately by traditional means. By identifying the components of complex dietary patterns that are linked to health status, researchers in CSM are actively involved in gathering together the scientific evidence that may help inform health policy relevant to clinical decision making and public health. 

Infection and Immunity

Mammalian responses to microbial / parasitic infection occur at many levels and include both the immune and metabolic pathways. Understanding those responses to infection in a mammalian host that are common, and those that are specific to a given infectious agent. Responses to inflammation are not restricted to infection, and the immune response profile through the course of disease processes provides a valuable source of complementary information in the context of systems biology. The linkage of the immune and metabolic responses provides an opportunity to gain a more comprehensive view of the biochemical processes that underlie response to infection and the influence of disease processes on mammalian health. Researchers in CSM have recently embarked on a programme of study focused on the interface of the immune system and metabolism using NMR and MS-based metabonomics in parallel with multiplexed cytokine profiling.

Infection and Immunity

Key members within Microbiome and Diet

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  • JOURNAL ARTICLE
    Biggs MB, Medlock GL, Moutinho TJ, Lees HJ, Swann JR, Kolling GL, Papin JAet al.,

    Systems-level metabolism of the Altered Schaedler Flora, a complete gut microbiota

    , ISME Journal, ISSN: 1751-7362

    The Altered Schaedler Flora (ASF) is a model microbial community with both in vivo and in vitro relevance. Here we provide the first characterization of the ASF community in vitro, independent of a murine host. We compared the functional genetic content of the ASF to wild murine metagenomes and found that the ASF functionally represents wild microbiomes better than random consortia of similar taxonomic composition. We developed a chemically-defined medium that supported growth of seven of the eight ASF members. To elucidate the metabolic capabilities of these ASF species—including potential for interactions such as cross feeding—we performed a spent media screen and analyzed the results through dynamic growth measurements and non-targeted metabolic profiling. We found that cross-feeding is relatively rare (32 of 3 570 possible cases), but is enriched between Clostridium ASF356 and Parabacteroides ASF519. We identified many cases of emergent metabolism (856 of 3 570 possible cases). These data will inform efforts to understand ASF dynamics and spatial distribution in vivo, to design pre- and probiotics that modulate relative abundances of ASF members, and will be essential for validating computational models of ASF metabolism. Well-characterized, experimentally tractable microbial communities enable research that can translate into more effective microbiome-targeted therapies to improve human health.

  • CONFERENCE PAPER
    Li JV,

    Metabonomics in Clinical Research

    , International Conference on Genomics
  • CONFERENCE PAPER
    Li JV,

    Short-term reciprocal diet exchanges impact colonic fermentation and hydrogenotrophic microbiota for native Africans consuming a typical Western diet and African Americans consuming a traditional African diet

    , Digestive Disease Week
  • JOURNAL ARTICLE
    Mayneris-Perxachs J, Bolick DT, Leng J, Medlock GL, Kolling GL, Papin JA, Swann JR, Guerrant RLet al.,

    Protein and zinc deficient diets modulate the murine microbiome and metabolic phenotype

    , American Journal of Clinical Nutrition, ISSN: 1938-3207

    Background: Environmental enteropathy, linked to undernutrition and chronic infections, affects the physical and mental growth of children in developing areas worldwide. Key to understanding how these factors combine to shape developmental outcomes is first understanding the effects of nutritional deficiencies on the mammalian system, including the effect on the gut microbiota.Objective: We dissect the nutritional components of environmental enteropathy by analyzing the specific metabolic and gut microbiota changes that occur in weaned mouse models of zinc or protein deficiency as compared to well-nourished controls. Design: Using a 1H NMR spectroscopy-based metabolic profiling approach with matching 16S microbiota analyses, the metabolic consequences and specific effects on the fecal microbiota of protein and zinc deficiency were probed independently in a murine model.Results: We find considerable shifts within the intestinal microbiota 14-24d post-weaning in mice maintained on a normal diet (including increases in Proteobacteria and striking decreases in Bacterioidetes). While the zinc deficient microbiota were comparable to the age-matched well-nourished profile, the protein-restricted microbiota remained closer in composition to the weaned enterotype with retention of Bacteroidetes. Striking increases in Verrucomicrobia (predominantly Akkermansia muciniphila) were observed in both well-nourished and protein-deficient mice 14d post-weaning. We find that protein malnutrition impairs growth and has major metabolic consequences (much more than zinc deficiency) that include altered energy, polyamine and purine/pyrimidine metabolism. Consistent with major changes in the gut microbiota, reductions in microbial proteolysis and increases in microbial dietary choline processing were observed.

  • JOURNAL ARTICLE
    Chilloux J, Dumas M-E, 2017,

    Are Gut Microbes Responsible for Post-dieting Weight Rebound?

    , CELL METABOLISM, Vol: 25, Pages: 6-7, ISSN: 1550-4131

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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