Irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by recurrent abdominal pain, that is associated with changes in stool frequency or stool form, in the absence of any organic disorder. Using ROME IV criteria, IBS is classified into four subtypes: IBS with predominant constipation (IBS-C), IBS with predominant diarrhea (IBS-D), with mixed bowel habits (IBS-M) or IBS, unsubtyped (IBS-U) which does not meet the criteria for IBS-C, D, or M [1]. Psychiatric comorbidities, such as anxiety, depression and somatization are common in patients with IBS (Figure 1).

Although IBS prevalence rates appear to differ between countries, it is estimated to affect around 1 in 10 people globally [2]. IBS can develop at any age, but its onset is often usually between age of 20 and 30. Women are almost twice as likely as men to have symptoms of IBS, they also report to feel more fatigue and psychiatric comorbidities. The quality of life of IBS patients is severely affected, interfering with their everyday life, frequently resulting in missing work or school. The economic burden of IBS on healthcare systems and society is significant, with both direct and indirect costs. Mean annual direct cost for IBS patients was calculated at 1363 Euros, in addition to patients missing on average 8-22 days of their work per year.

Pathophysiology of IBS is not fully understood, but in general it stems from impaired gut-brain axis, a bidirectional communication between the digestive tract and the central nervous system. It likely involves multiple underlying mechanisms, including peripheral factors, such as visceral hypersensitivity, altered motility, increased intestinal permeability and low-grade inflammation. Among central factors, altered processing of signals from the gut, hypervigilance, stress, as well as psychiatric comorbidities, such as anxiety and depression, seem to play an important role. During the last decade, increasing attention has been given to gut microbiota as a key player in IBS.

Microbiome in Irritable Bowel Syndrome

There are several lines of evidence, both from clinical studies and animal models, that implicate gut microbiota in IBS. First, bacterial gastroenteritis is the strongest risk factor for IBS, with 11-14% of patients developing chronic symptoms after acute infection with Campylobacter, Salmonella, Shigella, Escherichia coli or Clostridioides difficile infection [3]. Clinical data suggest that female sex, younger age, severity of infection and preceding psychiatric morbidity are risk factors for IBS. In addition, variants in genes related to the gut permeability, recognition of bacteria and innate immune responses have been identified.

Second line of evidence comes from clinical studies that demonstrated that certain antibiotics may improve symptoms in a proportion of patients with IBS [4]. On the other hand, clinical data also suggest that use of antibiotics, with likely subsequent intestinal dysbiosis, can lead to symptoms generation. And finally, multiple clinical trials have suggested that specific probiotics improve symptoms of IBS, such as abdominal pain, diarrhea or bloating.

The bacterial population thriving in the gut, collectively termed the gut microbiota is one of the major determinants of gut homeostasis. Accumulating data show that gut microbial composition and its metabolic activity differ between IBS patients and healthy controls, and that they associate with intestinal symptoms, as well as with anxiety and depression. However, the results from individual studies are highly variable and there seems to be no unique microbial profile that could be attributed to IBS. Despite this, a recent meta-analysis identified several microbial features, including increase in family Enterobacteriaceae, family Lactobacillaceae, and genus Bacteroides and decrease in uncultured Clostridiales, genus Faecalibacterium, and genus Bifidobacterium in patients with IBS compared to healthy controls (Figure 2) [5]. There are also multiple bacterial or host-microbial metabolites that are altered in patient with IBS, including phosphatidylcholine, dopamine, p-hydroxybenzoic acid, bile acids, tryptamine and histamine metabolites. However, all these findings are suggestive of association but not of causation.

The microbiota humanized mouse model is a valuable tool to establish the causal role of the gut microbiota in the IBS, and to study the underlying mechanisms leading to gut dysfunction. We used stool microbiota from patients with IBS-D and from age- and sex-matched healthy controls to colonize germ-free mice and studied them 4 weeks later. Mice colonized with IBS-D microbiota developed faster gastrointestinal transit, changes in gut barrier function and lowgrade intestinal inflammation, compared to mice colonized with microbiota from healthy controls [6]. Furthermore, mice that were colonized with microbiota from patients with comorbid anxiety also developed anxiety-like behavior, suggesting that microbiome transplantation from IBS patients into the murine host not only alters the gut function, but also impairs the gutbrain communication. These functional abbehanormalities
were associated with changes in multiple neuro-immune gene networks, as well as changes in many microbial and host metabolites. Interestingly, treatment with a probiotic normalized gastrointestinal transit and anxiety-like behavior in mice with IBS-D microbiota, which was associated with changes in microbiota profiles and bacterial indole production, reaffirming the notion that the gut microbiome plays a key role in the gut-brain communication [7].

Microbiota-gut-brain axis

The gut-brain axis is a bidirectional communication system between the gut and the brain integrated via neural, hormonal, and immunological signalling. Growing evidence suggests that the gut microbiota plays a key role in the communication between the gastrointestinal tract and the central nervous system, with most data being obtained from animal studies [8]. Germ-free mice have abnormal behavior, associated with changes in expression of multiple genes and chemistry in the brain, altered blood-brain barrier, changes in morphology of brain regions involved in control of mood and anxiety (amygdala and hippocampus), altered myelination profile and plasticity, as well as global defects in brain microglia. Most of these abnormalities are normalized after bacterial colonization. Microbiota also modifies behavior in conventional mice, as administration of non-absorbable antimicrobials can increase their exploratory behavior, together with changes in Brain- Derived Neurotrophic Factor (BDNF) in the hippocampus and amygdala. Changes in behavior induced by antibiotics have been also described in patients treated for acute infections or during eradication of chronic Helicobacter pylori infection; this condition was coined “antibiotic-induced psychosis”. Interestingly, a recent large population- based study found that use of antibiotics in early childhood was associated with an increased risk of developing mental health disorders in later life.

However, the most obvious case for the microbiota-gut-brain axis comes from patients with cirrhosis-associated hepatic encephalopathy that manifest with changes in behavior, mood and cognition [9]. These patients show dramatic improvement in brain function after administration of antibiotics or laxatives, and recent studies suggested that similar amelioration can be also achieved by fecal microbiota transplantation.

During recent years, multiple studies investigated gut microbiome in patients with psychiatric disorders, such as major depression and generalized anxiety, and found that the microbial profiles differed between patients and healthy controls. Furthermore, transferring microbiota from patients into germ-free or antibiotic treated rodents induced anxiety and depressive-like behanormalities viors. This raises question whether those probiotics, which showed beneficial effects on behavior and brain chemistry in animal models, could be used to treat patients with psychiatric diseases. The results of the few studies completed so far suggest that probiotics, if used as an adjunctive treatment, might improve symptoms in some patients with major depressive disorder [10].

We conducted a pilot RCT study in patients with IBS and comorbid depression to assess effects of a probiotic that showed beneficial effects on behavior and brain chemistry in several mouse models [11]. We found that compared to placebo, a 6-week probiotic treatment improved depression scores and overall symptoms of IBS. This was associated with changes in neuronal activation in the amygdala and other brain regions involved in mood control, as assessed by functional magnetic resonance imaging. This suggest that some probiotics may produce neuroactive metabolites that could be harnessed not only for treatment of patients with functional bowel disorders, but also for those with mental health issues. However, more rigorous clinical studies are needed to confirm and validate these findings.

Because of the overload imposed on their joints, overweight people are more prone to osteoarthritis. But how to identify those most at risk? The answer could lie in the gut microbiota which is involved in many inflammatory diseases, including osteoarthritis.

Lower microbial diversity in the gut of overweight patients with osteoarthritis

A prospective study was conducted in China on overweight people (25<BMI (sidenote: Body Mass Index.  Ratio of weight in kg to square of height in sq.m ) <30): 182 stool samples from 86 overweight patients with osteoarthritis (25 men and 61 women aged 50 to 72) and 96 overweight volunteers without osteoarthritis (40 men and 56 women aged 50 to 76) were sequenced (16S ribosomal RNA) to characterize their microbial composition. The study found a lower diversity and abundance in the gut microbiota of these overweight subjects in case of osteoarthritis, something that could indicate a disease-associated dysbiosis, according to the authors. The presence of 9 phyla was significantly different (higher or lower content, depending on the phylum) in case of osteoarthritis: for instance, the content of Firmicutes and Bacteroidetes, whose ratio is used as an indicator of dysbiosis, was significantly higher in patients with osteoarthritis. Moreover, 87 bacterial genera were different between overweight patients with and without osteoarthritis. All these bacteria allowed researchers to identify relevant osteoarthritis biomarkers.

Predicting the risk of osteoarthritis based on 7 biomarkers

Based on the previous results, the researchers identified 7 biomarkers found in the gut microbiota that could be used to develop a non-invasive tool for early assessment of the risk of osteoarthritis in overweight people: 3 over-represented bacterial genera in patients with osteoarthritis (Gemmiger, Klebsiella and Akkermansia) and 4 that are under-represented in those same patients (Bacteroides, Prevotella, Alistipes and Parabacteroides). Taken together, these biomarkers are able to precisely predict the risk of osteoarthritis (area under the curve of 83.36%). Among them the Bacteroides genus seems to play such a predominant role that the authors are considering it as a possible target for osteoarthritis treatment.

Providing scientific information for better health 

The Biocodex Microbiota Institute is an international scientific institution that aims to foster better health by spreading knowledge about human microbiota. To do so, the Institute addresses both healthcare professionals and the general public to raise awareness about the central role of this important organ.

As a pioneer in microbiota research, we have a responsibility to extend knowledge about microbiota 

For more than six decades, Biocodex has built a reputation as a pioneer and leader in the research and understanding of microbiota with the discovery and worldwide distribution of the probiotic Saccharomyces boulardii CNCM I-745. In 2017, the Microbiota Institute was born to answer the rising interest in microbiota and encourage the dissemination of scientific information concerning its key role in health.

With dedicated experts worldwide, we provide referenced and reliable information  

We are a group of microbiota enthusiasts accompanied by more than 20 international experts and a pool of scientific journalists. In other words, we have the skills and we have the content to make microbiota worth reading. 

The Institute has been recognized by peers and International medical societies such as the World Gastroenterology Organization.  

BMI 21.06

Cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of muscle mass that cannot be reversed by conventional nutritional support. The syndrome leads to progressive functional impairment, reduced tolerance to anticancer treatments and shorter survival times. Gastroesophageal cancer (GEC) patients are particularly at risk as their mechanical and digestive problems lead to loss of appetite and early satiety. Gut microbiota appears to play a crucial role in regulating certain aspects of cancer cachexia, such as satiety, appetite, host metabolism, systemic inflammation or modulation of the response to certain anticancer drugs. However, this role is impaired by cancer and most anticancer treatments that alter the intestinal barrier. Hence the idea to study the effects of fecal microbiota transplantation (FMT) on cachexia in GEC patients.

Study parameters: satiety, survival, and gut microbiota

This double-blind, randomized, controlled study was conducted on 24 cachectic patients with inoperable metastatic GEC undergoing palliative chemotherapy. These patients received allogenic FMT (treatment group; healthy overweight or obese donor) or autologous FMT (control group; donor = patient). The primary research objective was to evaluate the effect of FMT on satiety. Other characteristics of cachexia were also monitored, as well as the effectiveness of chemotherapy and survival. Lastly, exploratory analyses measured the effect of FMT on the composition of the gut microbiota.

No impact on satiety, but beneficial effect on disease progression

Contrary to expectations, allogenic FMT from a healthy obese donor did not improve the recipient's satiety or cachexia before chemotherapy. It nevertheless appears to have had a beneficial effect on disease progression: when compared to the control group, the 12 patients in the treatment group had a better disease control rate (based on RECIST criteria) at 12 weeks, and longer overall (365 vs. 227 days) and progression-free survival (204 vs. 93 days). Three patients in the control group and none in the treatment group died of cancer before the end of the study. The patients' fecal microbiota also changed after allogenic FMT, indicating proper engraftment of the donor microbiota despite chemotherapy. The researchers were unable to identify specific gut bacterial species associated with chemotherapy outcomes in the treatment group. FMT studies on a larger scale will be needed. Ultimately, the hope is for personalized treatments, via the administration of prebiotics and probiotics specifically adapted to a patient's microbiota to improve the effectiveness of anticancer drugs.

Cachexia brings forward images of weakened hunger strikers or patients in their last days of life. It is a state of extreme fatigue and emaciation and a sign of severe malnutrition or the terminal phase of certain diseases, such as gastroesophageal cancer. It is well known that gut microbiota seems to play a crucial role in the regulation of appetite, which cancer patients lack. This gave these researchers an idea, namely to implant their patients with gut flora from healthy obese donors since some of these microorganisms (sidenote: Microorganisms Living organisms that are too small to be seen with the naked eye. They include bacteria, viruses, fungi, archaea and protozoa, and are commonly referred to as “microbes”. What is microbiology? Microbiology Society. ) may have played a role in their weight gain.

No improvement in appetite but beneficial effect on cancer progression

Twenty-four cachectic patients with inoperable gastroesophageal cancer who were to receive palliative chemotherapy participated in the study. Twelve received flora from a healthy overweight or obese donor while the other twelve received their own microbiota (control group). No one knew who was receiving what so as not to influence the outcome. Contrary to the expectations of the researchers, allogenic FMT from a healthy obese donor did not improve the recipient's satiety or cachexia before chemotherapy. It nevertheless seems to have had a beneficial effect on the progression of the disease. Compared to the control group (which received its own flora), the cancer was better controlled in the 12 patients who received microbiota from an obese donor. Their survival was also improved. 

Gut bacteria and the effectiveness of chemotherapy? 

An analysis of their new fecal microbiota confirmed that the gut flora transplant was successful despite the chemotherapy that followed. However, it is impossible for the researchers to know at this stage whether certain specific gut bacterial species could lead to more effective chemotherapy treatment. Studies on a larger scale will be needed to find out more. While waiting for the next findings, follow the news of the Institute but do not under any circumstances try to make a home-made gut flora cocktail!

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Through its ability to connect millions of people, Twitter is currently the most popular form of social media used for healthcare communication. The Microbiota Institute joins the social media with one goal: raising a qualified community by creating an engaging dynamic around the latest microbiota news.

Building an international HCPs community around microbiota...

Latest scientific publications, experts’ interviews, thematic folders, live-tweet of conferences (WGO, ESPGHAN, etc.) ... Healthcare professionals will have access to a wide range of up-to-date scientific content. This new Twitter account (@Microbiota_Inst) is designed aiming to reach the widest community of health professionals who want to be up to date with the latest information on the microbiota field. Health professionals but not only. Thanks to this new communication channel, the Microbiota Institute wants to expand its audience by reaching recognized scholarly societies, healthcare students but also the specialized press, congresses, professional orders...

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By sharing accurate news about microbiota either from the Institute exclusive website content  (digest of research advances for clinical practitioner) or from other HCPs’ tweets, the Institute Twitter account aims to be recognized as a useful and trustful partner when it comes to research and clinical practice. Twitter is THE social network to follow in order to know and spread microbiota scientific knowledge. As a recognized international platform on that field, it was legitimate for the Institute to strengthen its presence on this channel.

About the Microbiota Institute

The Biocodex Microbiota Institute is an international scientific institution that aims to foster health through spreading knowledge about the human microbiota. To do so, the Institute addresses both healthcare professionals and the general public to raise their awareness about the central role of this still mis known organ of the body. 

^BMI-21.05