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Research Suggests Bile Acids Have Potential as a Therapy for Dysbiosis, Constipation, and Inflammatory Bowel Disease

Generally, when we think of bile, we first think of the role it plays in digestion. Produced by the liver and expelled into the digestive tract by the gallbladder, bile is the substance that serves to emulsify and break down dietary fats so that they can be absorbed in the small intestine. Thus, supplemental bile acids with meals may be important for individuals post-cholecystectomy or with fat malabsorption for other reasons. However, the effects and potential therapeutic benefits of bile acids in the body go far beyond this.

In the digestive tract, bile acids also affect the balance of flora and gut motility.[1],[2] Outside of the gut, they regulate many critical facets of physiology, including glucose and cholesterol metabolism; activating farnesoid X receptor (FXR), pregnane X receptor, the vitamin D receptor, and various G-protein-coupled receptors.[5] Evidence also suggests that bile acids affect neurological function, as well as the response of the hypothalamic–pituitary–adrenal axis.[6] Bile acids have even been suggested to be “novel therapeutic modalities in inflammation, obesity, and diabetes.”[7]

The Gut-Liver Axis

Monday, 17 September 2018 by
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Nature_Reviews_Gastroenterology_Hepatology_250x329The relationship between the contents, metabolites, barrier and immune response of the gut and organs and function in the body are becoming well understood, albeit there are many nuances associated with this relationship yet to be quantified.

One area in which the dynamic interaction between the gut and a specific organ is rapidly rising up the knowledge tree is the ‘gut and liver axis’. In large part this is due to the increase in the prevalence of liver related inflammation, of which non-alcoholic fatty liver disease (NAFLD) is becoming a global problem. For with the global rise of obesity and the associated metabolic syndrome, there has been an equally alarming and related rise in the incidence of NAFLD and non-alcoholic steatohepatitis (NASH) – the hepatic manifestations of the metabolic syndrome and the predominant chronic liver diseases worldwide[1]

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224231As functional disorders of the gut continue to increase in occurrence and develop in frequency across all population groups, a broad based review in the Journal Digestive Disorders published in Feb 2018 is a welcome chance to tease out elements of discord and dysbiosis that present opportunities for personalised intervention.[1]

Background and Summary: Traditionally, functional gastro­intestinal disorders (FGID), including functional dyspepsia or irritable bowel syndrome (IBS), are defined by more or less specific symptoms and the absence of structural or bio­chemical abnormalities that cause these symptoms. This concept is now considered to be outdated; if appropriate tests are applied, structural or biochemical abnormalities that explain or cause the symptoms may be found in many patients. Another feature of FGID are the highly prevalent psychiatric comorbidities, such as depression and anxiety.

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coverThere are trillions of microorganisms in the human microbiome — they outnumber their host’s cells substantially — and their exact role in health and disease is only now starting to be explored. Studies have found that people with non-alcoholic fatty liver disease have a different composition of bacteria in their gut from healthy individuals.[1],[2] However, it is as yet impossible to say why or what direct effect this has. Whatever the reason, changes in the microbiome are unlikely sufficient to cause disease. Instead, an emerging picture of liver disease and cancer sees their development as a process in which various factors — including a high-fat diet, alcoholism, genetic susceptibility and the microbiome — can each contribute to the progression from minor to severe liver damage, and from severe liver damage to cancer.

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Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease.[1] Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light: dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome.

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Conclusions Patients complaining of flatulence have a poor tolerance of intestinal gas, which is associated with instability of the microbial ecosystem.[1]

Significance of this study

What is already known on this subject?

  • Some patients specifically complain of excessive evacuation of gas per anus.
  • Intestinal gas content depends by-and-large on gas production by bacterial fermentation of unabsorbed substrates.
  • Diet influences anal gas evacuation and gut microbial composition.
  • A proportion of patients complaining of flatulence have increased number of gas evacuations, but the net volume of gas evacuated is within the normal range.
  • Flatulence is associated with abdominal symptoms.
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A paper out in PLOS this week has highlighted abnormalities in the bacterial compositions of the gut found in individuals diagnosed with autism. Whilst this is not a ground breaking a discovery as the authors suggest, it does add further qualification to the evolving recognition of the consistency of dysbiosis in individuals with autism.[1]

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By Michael Ash, BSc, DO, ND, F.DipIOn

One of my primary areas of research and expertise is the gut microbiota and its diverse impact on our health. Your liver receives nearly 70% of its blood supply from the intestine, and represents a first line of defence against gut-derived antigens. Intestinal bacteria—and the antigens they produce—play a key role in the maintenance of gut-liver axis health. Modulation of the gut microbiota to achieve and maintain symbiosis represents a new way to treat or prevent non-alcoholic fatty liver disease (NAFLD). Along with the concomitant use of tocotrienols and glycophospholipids, we may be starting to see the emergence of a truly profound intervention for a complex metabolic disease, using safe,natural compounds.

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An article in the New England Journal of Medicine, January 2013 explores the validity of faecal transplant therapy for the resolution of C. difficile therapy and reminds us that back in 1958 clinicians in Denver trialled this therapy to “re-establish the balance of nature” within the intestinal flora to correct the disruption caused by antibiotic treatment.[1]

Faecal Transplant (FT) and IBD

Tuesday, 25 September 2012 by | Comments: 2
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I have explored the role of appropriate transplantation in the resolution of MRSA infection that fails to resolve with antibiotic therapy, and have intimated that other conditions of the bowel and linked tissues may also benefit. The model is: that loss of mucosal tolerance underlies the pathology of inflammatory bowel disease and is also linked to irritable bowel syndrome. These altered states of function reflect a combination of environmental, genetic and emotional events that coalesce into a wide range of conditions.

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