Julien Tap

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.

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!

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.

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

(right click to enlarge image)

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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)

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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.

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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.

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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

A study¹ published in Molecular System Biology showed how gut microbiota could be used to detect colon cancer in combination with standard fecal occult blood test (FOBT). The potential is huge as the detection could be increased notably for early stage cancer (where curation have a better prognostic notably).

As a co-authors, I would like to give some additional insight regarding this paper like a “making of”, we could say. First of all, this study is the consequence of a fruitful collaboration between important institution between France (AP-HP) and Germany (EMBL, DKFZ). The most challenging part was to get samples in a right way directly from hospital, to improve current machine learning method to adapt them to metagenomics data and to devellop protocol to study the tumor environment.

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I defended my PhD in December 2009 and I knew that gut metagenomics will become more and more exiting with such big consortia such as MetaHIT and HMP. Combining with other gut microbiome initiatives within the international human microbiome consortium, they contributed to establish new resources, methods and clinical potential applications using metagenomics datasets.

I made a very rapid review here of huge step articles published during the last five years (I probably forget some of them).

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