Associations between usual diet and gut microbiota composition: results from the Milieu Interieur cross-sectional study

Background: Diet is widely recognized as one of the main modifiable drivers of gut microbiota variability, and its influence on microbiota composition is an active area of investigation. Objective: The present work aimed to explore the associations between usual diet and gut microbiota composition in a large sample of healthy French adults. Methods: Gut microbiota composition was established through sequencing of the 16S rRNA gene in stool samples from 862 healthy French adults of the Milieu Interieur study. Usual dietary consumptions were determined through the administration of a food-frequency questionnaire. The associations between dietary variables and alpha- and beta-diversity indexes and relative taxa abundances were tested using Spearman correlations, permutational ANOVAs, and multivariate analyses with linear models, respectively. Results: Foods generally considered as healthy (raw fruits, fish) were positively associated with alpha-diversity, whereas food items for which a limited consumption is generally recommended (fried products, sodas or sugary drinks, fatty sweet products, processed meats, ready-cooked meals, and desserts) were negatively associated with alpha-diversity. Fruits, fried products, ready-cooked meals, and cheese contributed to shifts within microbiota composition (beta-diversity). Our results also highlighted a number of associations between various food group intakes and abundances of specific phyla, genera, and species. For instance, the consumption of cheese was negatively associated with Akkermansia muciniphila abundance. Conclusions: This large-scale population-based study supports that the usual consumption of certain food items is associated with several gut microbial features, and extends the mechanistic arguments linking Western diet to an altered microbiota composition. These results provide new insights into the understanding of complex diet-gut microbiota relations, and their implications for host health deserve further investigation because altered microbiota diversity was consistently linked to increased risk of several health outcomes. This trial was registered at clinicaltrials.gov as NCT01699893.

Multidisciplinary Investigation of the Gut-Brain Ecosystem in a Model of Alzheimer's Disease

Arielle Louise Planchette

The search for an understanding of the causal elements that lead to neurodegenerative diseases has motivated researchers for decades. Today, Alzheimer's disease is the most prevalent form of dementia and affects approximately fifty million people worldwide, with only 5% of patients carrying causal genetic mutations. In recent years, studies of animal models as well as observations in humans have brought the gut microbiome to the forefront of AD research, as a significant contributor to the development of Alzheimer's disease. In fact, the gut microbiome is now understood to be a modulator of health and disease in numerous areas of physiology, including energy metabolism, immunity, endocrinology, and most relevant to this thesis, brain health and cognition. The gut microbiome is a complex environment composed of symbiotic bacteria, fungi and viruses (the microbiota) that produce a wide range of signalling molecules that are interpreted both by members of the microbiota and by the host (the microbiome). The host-gut interface is an ecosystem that consists of bi-directional signals and pressures applied by both constituents in order to maintain symbiotic homeostasis. Significant deleterious effects on health occur when homeostasis is lost, which may take place due to a variety of factors. These include host genetic factors and environmental factors, such as diet. Modulation of the gut microbiome has become a potentially viable therapeutic avenue for Alzheimer's disease, though it currently remains at the early stage of discovery. In this thesis, I characterize the evolution of Alzheimer's disease in the 5xFAD mouse model, with a focus on the gut microbiome and on cognitive decline and brain biochemistry. Gut microbiota modulaiton was implemented using germ-free and low-complexity bacterial cocktails, in which I outline the effects microbiota modulation on hallmarks of AD and provide insights into the metabolite profile of the brain altered by the microbiota and AD. The work in this thesis was equally motivated by the development of diagnostic tools using microscopy techniques. Biochemical assessments of disease status and progression provide information pertaining to "what" is interacting and "how much" this affects disease. With microscopy, we may gain the additional knowledge of "where" physiological constituents are and how they interact with the surrounding environment. I describe a novel multi-modal microscopy pipeline that enables the observation of signals of interest in large volumes and at high resolution with a capacity to cross-reference regions of interest in both modalities. The pipeline, known as gutOPT, consists of a sample preparation workflow compatible with mesoscale optical projection tomography (OPT) of fluorescently-labelled targets and subsequent imaging of pre-selected regions of interest in high-resolution modalities, such as confocal microscopy.

EPFL2022

Oral application of Escherichia coli bacteriophage: safety tests in healthy and diarrheal children from Bangladesh

Patrick Descombes

A T4-like coliphage cocktail was given with different oral doses to healthy Bangladeshi children in a placebo-controlled randomized phase I safety trial. Fecal phage detection was oral dose dependent suggesting passive gut transit of coliphages through the gut. No adverse effects of phage application were seen clinically and by clinical chemistry. Similar results were obtained for a commercial phage preparation (Coliproteus from Microgen/Russia). By 16S rRNA gene sequencing, only a low degree of fecal microbiota conservation was seen in healthy children from Bangladesh who were sampled over a time interval of 7 days suggesting a substantial temporal fluctuation of the fecal microbiota composition. Microbiota variability was not associated with the age of the children or the presence of phage in the stool. Stool microbiota composition of Bangladeshi children resembled that found in children of other regions of the world. Marked variability in fecal microbiota composition was also seen in 71 pediatric diarrhea patients receiving only oral rehydration therapy and in 38 patients receiving coliphage preparations or placebo when sampled 1.2 or 4 days apart respectively. Temporal stability of the gut microbiota should be assessed in case-control studies involving children before associating fecal microbiota composition with health or disease phenotypes.

Wiley-Blackwell2017

Thermal Stress Interacts With Surgeonfish Feces to Increase Coral Susceptibility to Dysbiosis and Reduce Tissue Regeneration

Leïla Ezzat

Dysbiosis of coral microbiomes results from various biotic and environmental stressors, including interactions with important reef fishes which may act as vectors of opportunistic microbes via deposition of fecal material. Additionally, elevated sea surface temperatures have direct effects on coral microbiomes by promoting growth and virulence of opportunists and putative pathogens, thereby altering host immunity and health. However, interactions between these biotic and abiotic factors have yet to be evaluated. Here, we used a factorial experiment to investigate the combined effects of fecal pellet deposition by the widely distributed surgeonfish Ctenochaetus striatus and elevated sea surface temperatures on microbiomes associated with the reef-building coral Porites lobata. Our results showed that regardless of temperature, exposure of P. lobata to C. striatus feces increased alpha diversity, dispersion, and lead to a shift in microbial community composition - all indicative of microbial dysbiosis. Although elevated temperature did not result in significant changes in alpha and beta diversity, we noted an increasing number of differentially abundant taxa in corals exposed to both feces and thermal stress within the first 48h of the experiment. These included opportunistic microbial lineages and taxa closely related to potential coral pathogens (i.e., Vibrio vulnificus, Photobacterium rosenbergii). Some of these taxa were absent in controls but present in surgeonfish feces under both temperature regimes, suggesting mechanisms of microbial transmission and/or enrichment from fish feces to corals. Importantly, the impact to coral microbiomes by fish feces under higher temperatures appeared to inhibit wound healing in corals, as percentages of tissue recovery at the site of feces deposition were lower at 30 degrees C compared to 26 degrees C. Lower percentages of tissue recovery were associated with greater relative abundance of several bacterial lineages, with some of them found in surgeonfish feces (i.e., Rhodobacteraceae, Bdellovibrionaceae, Crocinitomicaceae). Our findings suggest that fish feces interact with elevated sea surface temperatures to favor microbial opportunism and enhance dysbiosis susceptibility in P. lobata. As the frequency and duration of thermal stress related events increase, the ability of coral microbiomes to recover from biotic stressors such as deposition of fish feces may be greatly affected, ultimately compromising coral health and resilience.