Harry Sokol

• MD, PhD
• Professor (Full) at Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien)

Faecalibacterium has recently garnered attention for its potential health implications. To better understand its role, we developed and assessed real‐time PCR assays for detecting and quantifying various Faecalibacterium species in human stool samples from both healthy individuals and Crohn's disease patients, either in flare or remission. The assa...

Aging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-...

The gut microbiota constitutes a complex ecosystem essential for host defense against infection and maturation of the immune system. Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease, are characterized by a severe inflammation of the intestine, arising from dysregulated control of host-microbiota crosstalk. However,...

Background Fecal microbiota transplantation (FMT) is emerging as a potential treatment modality for individuals living with inflammatory bowel disease (IBD). Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical investigation. Notwithstanding differences in methodo...

The perturbation of the symbiotic relationship between microbes and intestinal immune system contributes to gut inflammation and Inflammatory Bowel Disease (IBD) development. The host mucosa glycans (glycocalyx) creates a major biological interface between gut microorganisms and host immunity that remains ill-defined. Glycans are essential players...

Background Faecalibacterium prausnitzii, a highly abundant bacterium in the human gut microbiota, has been linked to overall health and is notably decreased in pathological conditions, such as Inflammatory Bowel Disease (IBD). F. prausnitzii has shown anti-inflammatory properties in human and mouse models, notably through the induction of IL-10 sig...

Background Ileocecal resection (ICR) is a common procedure in Crohn’s disease (CD). Increasing evidence suggests ICR may be considered a first-line treatment for localized ileal CD to maintain long-term remission, rather than starting biologics. However, removal of the ileocecal valve affects bowel transit and disabling symptoms may arise. The aim...

Background Heat stress (HS) commonly occurring in summer has gradually become a factor threatening the reproductive performance of male dairy goats by reducing their fecundity. Despite the melatonin is applied to relieve HS, it is still unclear whether melatonin protects against reproductive damage induced by HS in dairy goats and how it works. The...

Background Detailed comparative assessment of procedure‐related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited. Aims We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure‐related factors associated wit...

The intestinal microbiota is increasingly recognized as a crucial player in the development and maintenance of various chronic conditions, including obesity and associated metabolic diseases. While most research focuses on the fecal microbiota due to its easier accessibility, the small intestine, as a major site for nutrient sensing and absorption,...

Background and aims Faecalibacterium prausnitzii , a highly abundant bacterium in the human gut microbiota, has been linked to overall health and is decreased in several pathological conditions, such as Inflammatory Bowel Disease (IBD). F. prausnitzii has shown anti-inflammatory properties in human and mouse models, notably through the induction of...

Impaired intestinal barrier function is a major feature of Crohn's disease (CD), leading to exacerbated inflammation in response to the microbiota. In this context, the translocation of intestinal bacteriophages (phages) and their effects on the host have been little investigated. We used phage fluorescence imaging coupled with ex-vivo and in-vitro...

Background Early complicated Crohn's disease (CD) may require ileal resection as first‐line treatment. Aim To evaluate the long‐term outcomes of patients who underwent early ileal resection. Methods We conducted a retrospective study in two inflammatory bowel diseases (IBD) referral centres, including patients with ileocaecal resection and segmen...

Systemic immune responses caused by chronic hypercholesterolaemia contribute to atherosclerosis initiation, progression and complications¹. However, individuals often change their dietary habits over time², and the effects of an alternating high-fat diet (HFD) on atherosclerosis remain unclear. Here, to address this relevant issue, we developed a p...

Preparing fecal microbiota transplants immediately after donation is resource-intensive, and a proportion are destroyed following abnormal screening results. We retrospectively compared two processes, frozen fecal preparation (FFP) and fresh native frozen preparation (FNFP), for clinical efficacy in the treatment of recurrent Clostridioides diffici...

Tryptophan (Trp) is an essential amino acid, whose metabolism is a key gatekeeper of intestinal homeostasis. Yet, its systemic effects, particularly on atherosclerosis, remain unknown. Here we show that high-fat diet (HFD) increases the activity of intestinal indoleamine 2, 3-dioxygenase 1 (IDO), which shifts Trp metabolism from the production of m...

Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of Faecalibacterium prausnitzii have been associated with a positive response to ICI in multiple cancer types. Here, based on fecal shotgun metagenomics data, we show in two independent cohorts of patients with non-small cell lung cancer and advanced melanoma that...

Increasing evidence suggests that the human blood hosts microbes including bacteria and eukaryotic viruses, which could have important implications for health. Bacteriophages of the blood are challenging to study and have been overlooked, but could translocate to this environment from different body-sites. We thus developed specific virome protocol...

Multivariate analysis is becoming central in studies investigating high-throughput molecular data, yet, some important features of these data are seldom explored. Here, we present MANOCCA (Multivariate Analysis of Conditional CovAriance), a powerful method to test for the effect of a predictor on the covariance matrix of a multivariate outcome. The...

The gut microbiome is a complex ecosystem whose members develop local interactions to form coherent functional communities. Variability in these communities, typically investigated through taxa co-abundance, might provide critical insights on the biological links between the gut microbiome and human phenotypes. However, existing methods to investig...

Background The etiology of inflammatory bowel disease (IBD) is unclear but involves both genetics and environmental factors, including the gut microbiota. Indeed, exacerbated activation of the gastrointestinal immune system toward the gut microbiota occurs in genetically susceptible hosts and under the influence of the environment. For instance, a...

Background and Aims: Tryptophan is an essential amino acid transformed by host and gut microbial enzymes into metabolites that regulate mucosal homeostasis through Aryl hydrocarbon receptor (AhR) activation. Alteration of tryptophan metabolism has been associated with chronic inflammation, however whether tryptophan supplementation affects the meta...

Background Despite the current therapeutic treatments including surgery, chemotherapy, radiotherapy and more recently immunotherapy, the mortality rate of lung cancer stays high. Regarding lung cancer, epigenetic modifications altering cell cycle, angiogenesis and programmed cancer cell death are therapeutic targets to combine with immunotherapy to...

Chronic digestive disorders are of increasing incidence worldwide with expensive treatments and no available cure. Available therapeutic schemes mainly rely on symptom relief, with large degrees of variability in patients’ response to such treatments, underlining the need for new therapeutic strategies. There are strong indications that the gut mic...

Mechanisms underlying the disruption of self-tolerance in acquired autoimmunity remain unclear. Immunoglobulin A (IgA) nephropathy is an acquired autoimmune disease where deglycosylated IgA1 (IgA subclass 1) auto-antigens are recognized by IgG auto-antibodies, forming immune complexes that are deposited in the kidneys, leading to glomerulonephritis...

The gut-lung axis is critical during viral respiratory infections such as influenza. Gut dysbiosis during infection translates into a massive drop of microbially produced short-chain fatty acids (SCFAs). Among them, butyrate is important during influenza suggesting that microbiome-based therapeutics targeting butyrate might hold promises. The butyr...

Dysbiosis corresponds to the disruption of a formerly stable, functionally complete microbiota. In the gut, this imbalance can lead to adverse health outcomes in both the short and long terms, with a potential increase in the lifetime risks of various noncommunicable diseases and disorders such as atopy (like asthma), inflammatory bowel disease, ne...

Background We aimed to compare the efficacy of different modalities of faecal microbiota transplantation (FMT) to induce clinical remission in patients with ulcerative colitis (UC). Methods We performed a systematic review and network analysis (random effects model) of randomized controlled trials including at least one arm of FMT in adult patient...

Background Adherent Invasive E. coli (AIEC) strains are found in one-third of patients with ileal Crohn’s disease (CD). To date, the bacterial genes involved in AIEC survival in the inflammatory environment are still unclear. Here, we systematically identify the genes of AIEC required for gut colonization and survival under the inflammatory conditi...

Background Alterations in gut microbiota composition and functions are involved in the pathogenesis of Inflammatory Bowel Disease (IBD) and the role of specific bacterial taxa has been particularly pointed out. The role of microbiota-derived metabolites, including those produced from tryptophan, are major actors in host-microbiota interactions in h...

The promising next-generation probiotic Faecalibacterium prausnitzii is one of the most abundant acetate-consuming, butyrate-producing bacteria in the healthy human gut. Yet, little is known about how acetate availability affects this bacterium’s gene expression strategies. Here, we investigated the effect of acetate on temporal changes in the tran...

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract that results from dysfunction in innate and/or adaptive immune responses. Impaired innate immunity, which leads to lack of control of an altered intestinal microbiota and to activation of the adaptive immune system, promotes a secondary inflammatory r...

Chronic obstructive pulmonary disease (COPD) is a major health issue primarily caused by cigarette smoke (CS) and characterized by breathlessness and repeated airway inflammation. NLRP6 is a cytosolic innate receptor controlling intestinal inflammation and orchestrating the colonic host–microbial interface. However, its roles in the lungs remain la...

The depletion of disruptive variation caused by purifying natural selection (constraint) has been widely used to investigate protein-coding genes underlying human disorders1-4, but attempts to assess constraint for non-protein-coding regions have proved more difficult. Here we aggregate, process and release a dataset of 76,156 human genomes from th...

Recessive diseases arise when both copies of a gene are impacted by a damaging genetic variant. When a patient carries two potentially causal variants in a gene, accurate diagnosis requires determining that these variants occur on different copies of the chromosome (that is, are in trans) rather than on the same copy (that is, in cis). However, cur...

Importance Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing. Objective To provide recommendations to improv...

Objectives Alterations in tryptophan (Trp) metabolism have been reported in inflammatory diseases, including rheumatoid arthritis (RA). However, understanding whether these alterations participate in RA development and can be considered putative therapeutic targets remains undetermined. In this study, we combined quantitative Trp metabolomics in th...

Many strains have been used and selected by the food industry for their capacities to ferment, produce flavors, or produce heterologous molecules. Very little is known about the diversity of foodborne yeasts and their potential effect on gut microbiota and gut health. We initiated a complete characterization of five strains belonging to five specie...

Background Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP. Methods We conduct...

Multivariate analysis is becoming central in studies investigating high-throughput molecular data, yet, some important features of these data are seldom explored. Here, we present MANOCCA (Multivariate Analysis of Conditional CovAriance), a powerful method to test for the effect of a predictor on the covariance matrix of a multivariate outcome. The...

Lung immune tone, i.e. the immune state of the lung, can vary between individuals and over a single lifetime, and its basis and regulation in the context of inflammatory responses to injury is not well understood. The gut microbiome, through the gut-lung axis, can influence lung injury outcomes but how the diet and microbiota affect lung immune ton...

Introduction Antibiotic effects on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the mycobiota, the fungal part of the microbiota and how the length of administration influences both microbiota. Here, we examined the effect of antibiotics (ATB) on the composition of bacterial and fungal...

Caspase recruitment-domain containing protein 9 (CARD9) is a key signaling pathway in macrophages but its role in atherosclerosis is still poorly understood. Global deletion of Card9 in Apoe-/- mice as well as hematopoietic deletion in Ldlr-/- mice increases atherosclerosis. The acceleration of atherosclerosis is also observed in Apoe-/-Rag2-/-Card...

In humans, many diseases are associated with alterations in gut microbiota, namely increases or decreases in the abundance of specific bacterial groups. One example is the genus Faecalibacterium. Numerous studies have underscored that low levels of Faecalibacterium are correlated with inflammatory conditions, with inflammatory bowel disease (IBD) i...

Objectives: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease associated with MEFV mutations. Disease phenotype and response to treatment vary from one patient to another despite similar genotype suggesting the role of environmental factors. We analyze the gut microbiota of a large cohort of FMF patients in r...

Background Most interactions between the host and its microbiota occur at the gut barrier, and primary colonizers are essential in the gut barrier maturation in the early life. The mother–offspring transmission of microorganisms is the most important factor influencing microbial colonization in mammals, and C-section delivery (CSD) is an important...

Background Several randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for ulcerative colitis, have recently been published, but with major variations in study design. These include differences in administered dose, route and frequency of delivery,...

Background: Familial Mediterranean Fever (FMF) is the most frequent monogenic autoinflammatory disease (AID). Some patients have persistent symptoms despite colchicine intake. Mast cells (MC) are innate immune cells involved in inflammatory conditions including AID. Their activation is responsible for various symptoms such as abdominal pain, bloat...

Background Tryptophan metabolism alterations have been reported in inflammatory diseases, including rheumatoid arthritis. However, understanding whether these alterations participate RA development and can therefore be considered as putative therapeutic targets remain undetermined. Objectives In this study, we combined quantitative Tryptophan meta...

Introduction Staphylococcus epidermidis is a commensal bacterium ubiquitously present on human skin. This species is considered as a key member of the healthy skin microbiota, involved in the defense against pathogens, modulating the immune system, and involved in wound repair. Simultaneously, S. epidermidis is the second cause of nosocomial infect...

Mouse models are key tools for investigating host-microbiome interactions. However, shotgun metagenomics can only profile a limited fraction of the mouse gut microbiome. Here, we employ a metagenomic profiling method, MetaPhlAn 4, which exploits a large catalog of metagenome-assembled genomes (including 22,718 metagenome-assembled genomes from mice...

Background: The aryl hydrocarbon receptor (AHR) is expressed in the intestine and liver, where it has pleiotropic functions and target genes. This study aims to explore the potential implication of AHR in cancer cachexia, an inflammatory and metabolic syndrome contributing to cancer death. Specifically, we tested the hypothesis that targeting AHR...

Fecal microbiota transplantation (FMT) has achieved satisfactory results in preventing the recurrence of Clostridioides difficile infection, but these positive outcomes have only been partially replicated in other diseases. Several factors influence FMT success, including those related to donors and recipients (including diversity and specific comp...

Immune checkpoint inhibitors (ICI) have deeply changed the therapeutic management of a broad spectrum of solid tumors. Recent observations showed that obese patients receiving ICIs might have better outcomes than those with normal weight, while obesity was historically associated with a worse prognosis in cancer patients. Of note, obesity is associ...

Background: In recent years, an increasing prevalence of obesity in inflammatory bowel disease (IBD) has been observed. However, only a few studies have focused on the impact of overweight and obesity on IBD-related disability. Aims: To identify the factors associated with obese and overweight patients with IBD, including IBD-related disability....

The gut microbiota is now recognized to be a key driver of mucosal inflammation in inflammatory bowel disease (IBD). Robust functional and compositional alterations of the gut microbiota have been described in IBD with a reduction in bacterial diversity, a reduction in some anti-inflammatory anaerobic bacteria, and an increase in bacteria with pro-...

Background: Effects of antibiotics on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the fungal microbiota (mycobiota). It is commonly believed that fungal load increases in the gastrointestinal tract following antibiotic treatment, but better characterization is clearly needed of how a...

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be ide...

Objective: To investigate host and gut-microbiota related Tryptophan metabolism in hand osteoarthritis (HOA). Methods: The baseline serum concentration of 20 Tryptophan metabolites was measured in 416 HOA patients in a cross-sectional analysis of the DIGICOD cohort. Tryptophan metabolites levels, metabolite-ratios and metabolism pathway activati...

Experimental and clinical evidence has demonstrated the potential of probiotic strains in the prevention or treatment of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). However, there is little data on what the methodology leading to the identification of such strains should be. In this work, we propose a new flowchart to ident...

Background and Purpose Gut bacteria metabolize tryptophan into indoles. Intestinal levels of the tryptophan metabolite indole‐3‐acetic acid are reduced in patients with alcohol‐associated hepatitis. Supplementation of indole‐3‐acetic acid protects against ethanol‐induced liver disease in mice. The aim of this study was to evaluate the effect of eng...

Background: Data on the role of the microbiota in cancer have accumulated in recent years, with particular interest in intratumoral bacteria. Previous results have shown that the composition of intratumoral microbiome is different depending on the type of primary tumour and that bacteria from the primary tumour could migrate to metastatic sites....

A substantial proportion of patients with hepatocellular carcinoma have to face up, sooner or later, to systemic therapy. The current standards as first line systemic therapies are either atezolizumab (anti-PD-L1) plus bevacizumab (anti-VEGF), or durvalumab (anti-PD-L1) plus tremelimumab (anti-CTLA-4). However, the median overall survival remains b...

Background The perturbation of the symbiotic relationship between microbes and the intestinal immune system contributes to Inflammatory Bowel Disease (IBD) development even years before diagnosis. However, the causes underlying the loss of gut microbial equilibrium (dysbiosis) associated with inflammation still remain unknow. The host glycocalyx (r...

Background Crohn’s Disease patients (CD) with early complicated behaviour (stenosis and/or fistula) are thought to have a more severe long-term disease course. To address this question, we focused on ileal CD that requires early intestinal resection after diagnosis. We aimed to assess the impact of the time to surgery from diagnosis on the risk of...