Julien Tap

Branches and ecological states of the gut microbiome: Mapping for future personalized nutritional and therapeutic interventions

Wed, 28 Jun 2023 18:00:00 +0000

A recent study published in Nature Communications¹ by researchers from Danone Research (Gif-sur-Yvette) and the University of San Diego in California examined 35,000 fecal samples from different populations and regions, making it one of the broadest studies of the gut microbiome.

The results revealed different communities within the gut microbiome, called “ecological states”, which are interconnected in larger groups called “microbiome branches”. These branches represent a continuum of microbiome configurations, dynamically linking local ecological states.

The researchers replicated this finding on several datasets, such as curatedMetagenomicData (CMD) and the American Gut Project (AGP), comprising diverse populations and age groups. Significant variations were observed in the different states of the microbiome in individuals belonging to the Bacteroides-enriched branch, indicating that the Faecalibacterium/Bacteroides ratio could serve as an indicator of microbiome instability.

The analysis also revealed the considerable impact of host factors such as age, body mass index, stool frequency, antibiotic use and region of birth on the gut microbiome. Dietary factors, including plant diversity, snack frequency, vegetable consumption and sweet foods, are associated with ecological states of the gut microbiome.

These findings highlight the importance of structuring microbiome data both locally and globally to better understand transitions between states and associations with health, diet and lifestyle. Thinking of the microbiome as branch-connected ecological states paves the way more than ever for personalized nutritional and therapeutic interventions.

Tap et al. Global branches and local states of the human gut microbiome define associations with environmental and intrinsic factors. 2023. Nature communications ↩

Fermentation microbiome projects

Sat, 01 Apr 2023 11:45:00 +0000

Here are a list of fermented foods related projects where I am involved:

Grand Défi Ferments du Futur

Ferments du Futur is a public-private partnership built to accelerate research and innovation in ferments, fermented foods and biopreservation, thereby promoting

DOMINO

DOMINO is a Horizon Europe funded research project aiming to attribute health benefits to traditional fermented foods, and to develop novel plant-based fermented

MetaSimFood

The objective of Metasimfood project is develop generic scientific approaches to help rapidly understand and anticipate the effects of multiple and complex changes related to modifications associated with fermented food production (sustainability issues). One of main guideline is to learn how to use the biodiversity of food microbiota as a lever.

PIMENTO

The challenge of COST-PIMENTO (CA20128-Promoting Innovation of ferMENTed fOods) is to federate the scientific community and key stakeholders working on FF. The idea is to collectively advance scientific evidence of their health benefits, building benefits/risk approach 5 order to promote multi-modal innovation and meet the expectations of European communities.

10 years of research about IBS, gut microbiota and fermented product at Danone Research - what do we found?

Thu, 05 Jan 2023 10:00:00 +0000

Irritable bowel syndrome (IBS) is a common disorder characterized by abdominal pain, bloating, and changes in bowel habits. The role of the gut microbiota in IBS has been increasingly recognized, and several studies have identified alterations in the gut microbial composition and function in IBS patients.

In a study by Tap et al. (2017), the authors identified an intestinal microbiota signature associated with the severity of IBS using 16S rRNA gene sequencing. They found that IBS patients had a distinct microbiota composition compared to healthy controls, with lower relative abundances of several butyrate-producing bacteria, including Faecalibacterium, Roseburia, and Eubacterium. In a follow-up study, Bennet et al. (2018) found that IBS patients had an altered intestinal antibacterial gene expression response profile, which was linked to bacterial composition and immune activation.

The gut microbiota may also play a role in the secretion of chromogranins and secretogranins, which are markers of enteroendocrine cells in the gut. Sundin et al. (2018) found that fecal levels of chromogranins and secretogranins were linked to the fecal and mucosal bacterial composition of IBS patients and healthy subjects.

The gut microbiota has also been linked to brain functional connectivity and gastrointestinal sensorimotor function in IBS patients. Labus et al. (2019) used tripartite network analysis to show an association between gut microbial Clostridia and brain functional connectivity in IBS patients.

Le Nevé et al. (2019) examined the role of the gut microbiota in the response to a fermented milk product in IBS patients. They found that fasting breath hydrogen and the metabolic potential of the gut microbiota were associated with the response to the fermented milk product. In a separate study, Le Nevé et al. (2020) found that a fermented milk product containing Bifidobacterium lactis CNCM I-2494 and lactic acid bacteria improved gastrointestinal comfort in response to a challenge diet rich in fermentable residues in healthy subjects. The effects of the fermented milk product on the gut microbiota were further investigated in a metatranscriptomic analysis by Oyarzun et al. (2022). They found that the fermented milk product mitigated the effects of a flatulogenic diet on gas-related symptoms in several ways, including the depletion of gas-producing bacteria and increased hydrogen to methane conversion, upregulation of certain metabolic activities, and a more connected microbial ecosystem.

Nevé et al. (2020) also examined the effects of a fermented milk product containing Bifidobacterium lactis CNCM I-2494 on the tolerance of a plant-based diet in patients with disorders of gut-brain interactions (DGBI), which include IBS and functional dyspepsia. They found that the fermented milk product improved tolerance to a plant-based diet in these patients, as well as reducing gastrointestinal symptoms and exhaled hydrogen.

The diet-microbiota-symptom interactions in IBS were further explored in a study by Tap et al. (2021). The authors used a food diary and shotgun metagenomic analysis to examine the diet and gut microbiome in 149 IBS patients and 52 healthy controls. They found that individuals with severe IBS had a higher intake of poorer-quality food items during main meals and that covariations between the gut microbiota at the subspecies level and diet could be explained by IBS symptom severity, exhaled gas levels, glycan metabolism, and the ratio of meat to plant intake. They also found evidence that IBS severity is associated with altered gut microbiota hydrogen function, which is correlated with microbiota enzymes involved in animal carbohydrate metabolism.

Polster et al. (2021) used a novel integrative analysis pipeline to examine the microbiota-host interactions and their link to symptoms in IBS. They found that there were distinct differences in the gut microbiota of IBS patients compared to healthy controls and that these differences were associated with specific IBS symptoms.

In summary, several studies have identified alterations in the gut microbiota composition and function in IBS patients and have provided evidence for the role of the microbiota in IBS symptoms. Some studies have also shown that fermented products, such as fermented milk products, may have a beneficial effect on IBS symptoms and the gut microbiota in IBS patients. However, more research is needed to fully understand the mechanisms underlying these associations and to determine the optimal fermented products and probiotic strains for the management of IBS symptoms. Targeted therapies targeting the gut microbiota may also be a promising approach for the management of IBS.

References

Tap J, Derrien M, Törnblom H, Brazeilles R, Cools-Portier S, Doré J, Störsrud S, Le Nevé B, Öhman L, Simrén M. Identification of an Intestinal Microbiota Signature Associated With Severity of Irritable Bowel Syndrome. Gastroenterology. 2017 Jan;152(1):111-123.e8. doi: 10.1053/j.gastro.2016.09.049. Epub 2016 Oct 7. PMID: 27725146.
Bennet SMP, Sundin J, Magnusson MK, Strid H, Tap J, Derrien M, Le Nevé B, Doré J, Törnblom H, Simrén M, Öhman L. Altered intestinal antibacterial gene expression response profile in irritable bowel syndrome is linked to bacterial composition and immune activation. Neurogastroenterol Motil. 2018 Dec;30(12):e13468. doi: 10.1111/nmo.13468. Epub 2018 Sep 17. PMID: 30230134.
Sundin J, Stridsberg M, Tap J, Derrien M, Le Nevé B, Doré J, Törnblom H, Simrén M, Öhman L. Fecal chromogranins and secretogranins are linked to the fecal and mucosal intestinal bacterial composition of IBS patients and healthy subjects. Sci Rep. 2018 Nov 14;8(1):16821. doi: 10.1038/s41598-018-35241-6. PMID: 30429499; PMCID: PMC6235916.
Labus JS, Osadchiy V, Hsiao EY, Tap J, Derrien M, Gupta A, Tillisch K, Le Nevé B, Grinsvall C, Ljungberg M, Öhman L, Törnblom H, Simren M, Mayer EA. Evidence for an association of gut microbial Clostridia with brain functional connectivity and gastrointestinal sensorimotor function in patients with irritable bowel syndrome, based on tripartite network analysis. Microbiome. 2019 Mar 21;7(1):45. doi: 10.1186/s40168-019-0656-z. PMID: 30898151; PMCID: PMC6429755.
Le Nevé B, Derrien M, Tap J, Brazeilles R, Cools Portier S, Guyonnet D, Ohman L, Störsrud S, Törnblom H, Simrén M. Fasting breath H2 and gut microbiota metabolic potential are associated with the response to a fermented milk product in irritable bowel syndrome. PLoS One. 2019 Apr 4;14(4):e0214273. doi: 10.1371/journal.pone.0214273. PMID: 30946757; PMCID: PMC6448848.
Le Nevé B, de la Torre AM, Tap J, Derrien M, Cotillard A, Barba E, Mego M, Nieto Ruiz A, Hernandez-Palet L, Dornic Q, Faurie JM, Butler J, Merino X, Lobo B, Batet FP, Accarino A, Pozuelo M, Manichanh C, Azpiroz F. A Fermented Milk Product with B. Lactis CNCM I-2494 and Lactic Acid Bacteria Improves Gastrointestinal Comfort in Response to a Challenge Diet Rich in Fermentable Residues in Healthy Subjects. Nutrients. 2020 Jan 25;12(2):320. doi: 10.3390/nu12020320. PMID: 31991794; PMCID: PMC7071254.
Polster A, Öhman L, Tap J, Derrien M, Le Nevé B, Sundin J, Törnblom H, Cvijovic M, Simrén M. A novel stepwise integrative analysis pipeline reveals distinct microbiota-host interactions and link to symptoms in irritable bowel syndrome. Sci Rep. 2021 Mar 9;11(1):5521. doi: 10.1038/s41598-021-84686-9. PMID: 33750831; PMCID: PMC7943560.
Tap J, Störsrud S, Le Nevé B, Cotillard A, Pons N, Doré J, Öhman L, Törnblom H, Derrien M, Simrén M. Diet and gut microbiome interactions of relevance for symptoms in irritable bowel syndrome. Microbiome. 2021 Mar 26;9(1):74. doi: 10.1186/s40168-021-01018-9. PMID: 33771219; PMCID: PMC8004395.
Nevé BL, Martinez-De la Torre A, Tap J, Ruiz AN, Derrien M, Cotillard A, Faurie JM, Barba E, Mego M, Dornic Q, Butler J, Merino X, Lobo B, Batet FP, Pozuelo M, Santos J, Guarner F, Manichanh C, Azpiroz F. A Fermented Milk Product Containing B. lactis CNCM I-2494 Improves the Tolerance of a Plant-Based Diet in Patients with Disorders of Gut-Brain Interactions. Nutrients. 2021 Dec 18;13(12):4542. doi: 10.3390/nu13124542. PMID: 34960094; PMCID: PMC8709116.
Oyarzun I, Le Nevé B, Yañez F, Xie Z, Pichaud M, Serrano-Gómez G, Roca J, Veiga P, Azpiroz F, Tap J, Manichanh C. Human gut metatranscriptome changes induced by a fermented milk product are associated with improved tolerance to a flatulogenic diet. Comput Struct Biotechnol J. 2022 Apr 5;20:1632-1641. doi: 10.1016/j.csbj.2022.04.001. PMID: 35465165; PMCID: PMC9014321.

Futuristic fermented food for Gut Microbiota

Fri, 30 Sep 2022 14:45:00 +0000

What if we ask an AI to generate a realistic picture about futuristic fermented foods that keep microbiota to stay in an healthy state?

This is what I tried with midjourney. Midjourney is a proprietary artificial intelligence program that creates images from textual descriptions.

here is the result :

it looks scary but still inspiring!

Human gut metatranscriptome changes induced by a fermented milk product are associated with improved tolerance to a flatulogenic diet

Fri, 08 Apr 2022 18:00:00 +0000

In a recent study¹, we combined taxonomic, functional, and network analysis from shotgun metatranscriptomics analysis of fecal samples, which were collected during the ingestion of a habitual diet and two series of a 3-day high-residue challenge diet, before and following 28-days of fermented milk product (FMP) consumption.

FMP consumption was associated with the depletion of gas-producing bacteria and increased hydrogen to methane conversion. It also led to the upregulation of activities such as replication and downregulation of functions related to motility and chemotaxis.

We showed new mecanistic insights about how active FMP may help to improve disgestive confort under high-residue challenge diet.

Oyarzun et al. Human gut metatranscriptome changes induced by a fermented milk product are associated with improved tolerance to a flatulogenic diet. 2022. Cell Host Microbe ↩

Diet and gut microbiome interactions of relevance for symptoms in irritable bowel syndrome

Fri, 26 Mar 2021 18:00:00 +0000

We published a study entitled “Diet and gut microbiome interactions of relevance for symptoms in irritable bowel syndrome” in Microbiome journal.

First, we used a food tree approach¹ to explore dietary data from our cohort. We added a specific nutrient layer to this food tree and computed FSA-NPS diet index (used now to compute NutriScore in front pack food in Europe).

We notably observed that individuals with severe IBS symptoms consumed a higher amount of lower-quality food items during their main meals than healthy controls.

Thank to shotgun metagenomics combining with MSP pangenomes², we were able to study diet interactions at subspecies levels. We found an interesting signal with Eubacterium rectale flagelin and diet for instance.

Using co-inertia analysis between unifrac food tree and MSP at subspecies levels combining with machine learning, we were able to predict meat/plant ratio, exhaled gas and symptoms severity.

As we found some signals in exhaled gas, carbohydrate metabolism and IBS severity, we aimed to do a specific focus on gut microbial hydrogenase and found a differential signal that correlate with meat/mucin associated CAZy.

Our study³ provides an unprecedented resolution of diet-microbiota-symptom interactions and ultimately guides new interventional studies that aim to identify gut microbiome-based nutritional recommendations for the management of gastrointestinal symptoms.

Johnson AJ et al. Daily sampling reveals personalized diet-microbiome associations in humans. 2019. Cell Host Microbe ↩
Plaza Oñate F et al. MSPminer: abundance-based reconstitution of microbial pan-genomes from shotgun metagenomic data.. 2019. Bioinformatics ↩
Tap J et al. Diet and gut microbiome interactions of relevance for symptoms in irritable bowel syndrome.2021. Microbiome ↩

Keystone Cork 2019 Microbiome

Sun, 06 Oct 2019 18:00:00 +0000

We presented a study entitled “Gut microbiome hysteresis is associated with durable mucosal alterations” during the Keystone Symposia poster session helded at Killarney : “Microbiome: Therapeutic Implications”

(right click to enlarge image)

Abstract

Introduction. The factors governing gut microbiome resilience upon ecological stressors are poorly understood. Inflammation and poor-quality diets are thought to trigger microbiota critical transition that may contribute to the development of non-communicable diseases in humans. Here, we explored the consequences of repeated cycles of intestinal inflammation on gut microbiome dynamics in a rat model.

Methods. We designed a time course experiment to capture the variations in body weight and gut microbiome (10 time points per rat) prior, during and after 3 cycles of Dextran Sodium Sulfate (DSS) challenge followed by 36 days of recovery phase. 60 rats were randomized to six groups of DSS doses (from 0 to 3%). Colonic histology and fecal lipocalin were assessed at sacrifice and analyzed with dose-response modeling. In addition to microbiome diversity analysis, Dirichlet-multinomial mixture and hysteresis models were used.

Results. We observed higher levels of selected markers of intestinal inflammation (mononuclear cell infiltration, distal histological score and fecal lipocalin) after the final recovery period for the rats exposed to the highest doses of DSS (1% to 3%), suggesting a critical transition associated with durable mucosal alterations. An analysis of the gut microbiome dynamics identified Akkermansia as a major tipping element following a bimodal distribution. This finding, together with microbiome hysteresis modeling, resulted in the identification of resistant, resilient and non-resilient microbiome trajectories for high DSS doses. Rats with non-resilient microbiomes displayed mucosal damages relative to those with resilient microbiome profiles.

Conclusion. This study provides a thorough exploration of microbiome dynamics prior and after an induced chronic inflammation. Our results support the hypothesis that some individuals are more prone to critical transition due to their hysteretic microbiome. In the future, hysteresis modelling of human gut microbiome may help design new solutions to prevent critical transitions associated with host physiology durable alterations.

Authors : Julien Tap, Sebastian Burz, Aurélie Cotillard, Julie Cadiou, Hervé Blottière, Joël Doré, Patrick Veiga, Muriel Derrien

You may found the source code on github

Predict the gut microbiota resistome

Tue, 27 Nov 2018 10:00:00 +0000

The intestinal microbiota is considered to be a major reservoir of antibiotic resistance determinants (ARDs) that could potentially be transferred to bacterial pathogens via mobile genetic elements. A collaboration between several research institute including INRA, AP-HP and Institut Pasteur succeed to predict more than 6,000 ARDs from the gut microbiota using protein structural model.

A study¹ published in Nature Microbiology in November 2018 showed that a new developped method based on 3D structural modeling was able to predict 10-fold more ARDS genes than previous studies. To confirm those prediction, several distant hit were tested using gene synthesis confirming their ability to confer antibiotic resistance. In addition, authors were able to cluster individuals into six resistotypes very closely related to previous enterotypes.

Main findings

First, authors developed and validated an annotation method on the basis of a three-dimensional structure, leading to the prediction of 6,095 ARDs in a catalogue of 3.9 million proteins from the human intestinal microbiota
Secondly, authors found little evidence supporting their transfer between species.
Third, according to the composition of their resistome, authors were able to cluster subjects from the MetaHIT cohort into six resistotypes that were connected to the previously described enterotypes..
Finally, authors found that the relative abundance of pdARDs was positively associated with gene richness, but not when subjects were exposed to antibiotics.

Behind the scene

The first author, Etienne “ARDs hunter” Ruppe, explained how ideas behind the paper came in a blog post published in Nature community.

Ruppe E, Ghozlane A, Tap J et al. Prediction of the intestinal resistome by a three-dimensional structure-based method.2018. Nature microbiology ↩

Symptoms severity of irritable bowel syndrome associated with gut microbiota

Sat, 05 Nov 2016 12:03:00 +0000

Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder in western societies, characterized by chronic abdominal pain and discomfort. It affects about 11% of the adult population and strongly impairs quality of life, social function, work productivity and brings substantial costs to health-care services. The etiology of IBS remains poorly understood and the search for biomarkers is ongoing. It is now well accepted that IBS is a disorder involving multiple pathophysiological mechanisms where composition of gut microbiota has been proposed as one of the potentially important factors.

A study¹ published in Gastroenterology in Octobre 2016 showed how some gut microbiota species were associated with IBS symptoms severity. Information on the fecal and mucosa-associated microbiota of patients with IBS were collected. The study evaluated whether these were associated with symptoms of gastrointestinal discomfort with a focus on the severity of symptoms.

Main findings

Authors showed firstly that gut enterotypes distribution changed along the severity gradient.
Secondly, using machine learning technique, authors picked up 90 microbial species to model a gut microbiota signature for IBS symptoms severity.
Using co-inertia analysis to study the gut microbiome, authors showed that this signature was associated with anxiety and depression, a decrease of bacterial richness and a lower exhaled methane.
The enterotype more prevalent in Healthy subject was Prevotella enriched type.

In addition, this study showed also that fecal microbiota covariated with mucosal microbiota despite a different microbiota composition. Using classical approaches, no major differences were found in fecal microbiota abundance or composition between patients with vs without IBS. A computational statistical technique-like machine learning procedure allowed us to reduce the 16S rRNA data complexity into a microbial signature for severe IBS, consisting of 90 bacterial operational taxonomic units. the robustness of the intestinal microbial signature were confirmed for severe IBS in the validation set. The signature was able to discriminate between patients with severe symptoms, patients with mild/moderate symptoms, and healthy subjects.

Using this intestinal microbiota signature, IBS symptom severity was found to be inversely associated with microbial richness, exhaled CH4, presence of methanogens, and enterotypes enriched with Clostridiales or Prevotella species. This microbiota signature could not be explained by differences in diet or use of medications.

Tap J, Derrien M et al. Identification of an Intestinal Microbiota Signature Associated With Severity of Irritable Bowel Syndrome.2016. Gastroenterology ↩

Gut microbiota richness promotes its stability upon increased dietary fibre intake

Fri, 29 Jan 2016 12:03:00 +0000

A study¹ published in Environmental Microbiology in September 2015 showed how gut microbiota stability depend of its richness when individuals took high fiber diet. Using various methods to study the gut microbiome, we observed that higher microbiota richness was associated with higher microbiota stability upon increased dietary fibre intake. Metatranscriptomics analysis showed that numerous glycan metabolism were also modulated including carbohydrate active enzymes. Individual with higher richness and higher stability had higher diversity of short chain fatty acid comprising acetate, propionate and butyrate but also caproate and valerate compared to the lower richness microbiota.

In addition, this study showed that a simple food vegetable questionaire summarized into a vegetable diversity index could be predictive of gut microbiota richness. Gut microbiota richness should definitly be taken into account before any nutritional intervention.

See also INRA Press release: An original study in healthy individuals: impact of a high-fibre diet on the gut microbiota

Tap J et al. Gut microbiota richness promotes its stability upon increased dietary fibre intake in healthy adults.2015. Environmental Microbiology 17: 4954–4964 ↩