22017Nov

Bugs, bowel movements and bloating

Bugs, bowel movements and bloating - Can our gut flora cause constipation?

The relevance of the gut flora, or microbiome, and its active role in chronic gastrointestinal disorders has been well documented in the scientific literature over the past years. A direct relation between bacteria produced methane and constipation has been determined and observed (1).

What is methane, its role and how is it produced?

Methanogenesis (the production of the gas methane) in microbes, is a form of anaerobic respiration (respiration in an environment without oxygen, like our intestine for example) and the gas methane is a product of this process. Methanogens (the name of this specific group of bacteria) do not use oxygen to respire, in fact, this is toxic to them and inhibits their growth (2).

In the intestine one specific methanogen, Methanobrevibacter Smithii, has been identified and it’s presence has been associated to constipation (1). In fact, the presence of the gas methane in the intestine, causes a significant reduction of the motility or, in other words, causes constipation. Studies have shown that the higher the level of methane in the intestine, the more severe the constipation is in patients (3).


It has been proven that reducing the levels of methane in the intestine improves the symptoms of constipation and bloating in patients (4-6).

What are the therapeutic options to reduce elevated levels of methane in the intestine?

A well-studied, effective and safe way to reduce the levels of methane in the intestine is to eliminate the source of the methane production, or in other words, kill the methanogenic bacteria with antibiotics. The ideal antibiotic then is a non-absorbable, gut targeted antibiotic, whose aims should not be to eradicate the entire bacterial flora but rather to modify the intestinal microecology to get symptoms relief (7,12).

Rifaximin is a product of synthesis experiments designed to modify the parent compound, rifamycin, to achieve low gastrointestinal absorption while retaining good antibacterial activity (8-10). Both experimental and clinical pharmacology have clearly shown that this compound is a poorly absorbed antibiotic with a broad spectrum of antibacterial activity, covering Gram-positive and Gram-negative microorganism, both aerobes and anaerobes (8-11). Rifaximin in combination with neomycin (another poorly absorbed antibiotic) has demonstrated the highest efficacy rate in improving bloating and constipation related to elevated levels of methane in the small intestine (4-6).


Treatments in Development 

A new drug, SYN-010, is currently under development in the US by the company Synthetic Biologics. SYN-010 is a modified-release formulation of lovastatin lactone that is intended to reduce methane production by certain microorganisms (M. smithii) in the gut while minimizing disruption to the microbiome to treat an underlying cause of irritable bowel syndrome with constipation (IBS-C). You can watch the video of SYN-010 mechanism of action by clicking the following link: HERE

Methane and SIBO (Small Intestinal Bacterial Overgrowth) 

Elevated levels of methane, could be related also to a condition called SIBO (Small Intestine Bacteria Overgrowth). SIBO is a heterogeneous syndrome characterized by an increased number and/or abnormal type of bacteria in the small bowel, and it is a well-recognized cause of mal-digestion and malabsorption. SIBO represents an umbrella term, under which some different functional (e.g. irritable bowel syndrome, chronic constipation, diarrhea) or organic (e.g. inflammatory bowel disease, coeliac disease, diverticular disease, etc.) conditions can be included, as – in each of them – bacterial proliferation (and consequent inflammation) may, at least in part, trigger similar abdominal symptoms (12).


How can I know if I have elevated levels of methane in my intestine and if that is the cause of my constipation?

Breath tests represent a valid and non-invasive diagnostic tool. The rationale of hydrogen / methane breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation (hydrogen and methane) diffuses into the blood and is excreted by breath, where it can be quantified easily (13).


REFERENCES:

  1. Kunkel, et al. Dig Dis Sci, 2011
  2. Thauer, R. K. (1998). "Biochemistry of Methanogenesis: a Tribute to Marjory Stephenson". Microbiology. 144: 2377–2406. doi:1099/00221287-144-9-2377
  3. Pimentel, et al. Am J Physiol, 2006
  4. Low, et al. Gastroenterol and Hepatol 2010
  5. Pimentel, et al. Dig Dis Sci, 2014
  6. Pimentel, et al. ACG, 2013
  7. Scarpignato C, Gatta L. Commentary: towards an effective and safe treatment of small intestine bacterial overgrowth. Aliment Pharmacol Ther 2013; 38: 1409–10.
  8. Marchi E, Montecchi L, Venturini AP, Mascellani G, Brufani M, Cellai L. 4Deoxypyrido[1’,2’:1,2]imidazo[5,4-c] rifamycin SV derivatives. A new series of semisynthetic rifamycins with high antibacterial activity and low gastroenteric absorption. J Med Chem 1985; 28: 960–3. 10.
  9. Scarpignato C, Pelosini I. Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy 2005; 51(Suppl. 1): 36–66. 11.
  10. Calanni F, Renzulli C, Barbanti M, Viscomi GC. Rifaximin: beyond the traditional antibiotic activity. J Antibiot 2014; 67: 667–70.
  11. Adachi JA, Dupont HL. Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders. Clin Infect Dis 2006; 42: 541–7.
  12. Gatta, C. Scarpignato: Systematic review with meta-analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Aliment Pharmacol Ther 2017; 45: 604–616
  13. Gasbarrini et al. Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference. Aliment Pharmacol Ther 29 (Suppl. 1), 1–49

Patient stories provided by Dr Chris Fraser 

Dr Fraser is a Consultant Gastroenterologist and Honorary Senior Lecturer at the Royal Infirmary of Edinburgh, Spire Edinburgh Hospitals (Murrayfield and Shawfair Park) and The Edinburgh Clinic, Scotland. He was previously Consultant Gastroenterologist at St Mark's Hospital, Harrow for 10 years before relocating to Edinburgh. He qualified MB ChB from Edinburgh University in 1992 with post graduate training in Aberdeen, Birmingham, Manchester and London. He achieved MRCP in 1996, was awarded an MD in 2004 for studies in the neurophysiologic control of swallowing and became FRCP in 2009. He undertook the 1st advanced endoscopy fellowship at The Wolfson Unit for Endoscopy at St Mark's Hospital in 2003. While at St Mark's, he was a nationally accredited NHS bowel cancer screening specialist in colonoscopy. He continues to perform colonoscopy for the Scottish National Bowel Cancer Screening Programme in Edinburgh.

Dr Fraser consults at The Spire Murrayfield and Shawfair Park Hospitals and The Edinburgh Clinic. Dr Fraser's endoscopic procedures are carried out in The Spire Shawfair Park Endoscopy Unit. Dr Fraser has worked in collaboration with The Functional Gut Clinic for the last 3-years and has been instrumental in helping to bring The Functional Gut Clinic to Scotland.


Patient Stories - Methane and Constipation 

Patient story 1:

KIRSTY IS A 44-YEAR OLD FEMALE PATIENT WITH LONG STANDING CONSTIPATION. HER HYDROGEN AND METHANE BREATH TEST SHOWED A BASELINE METHANE READING OF 62 PARTS PER MILLION (PPM) – NORMAL IS <10PPM

For as long as I can remember, I attempted to get help from my GP over 20 years ago, I was told I had a very slow transient time (this was determined by a colonic transit study where radio-opaque markers were swallowed followed by an xray a week later), and basically I was left to get on with it.

Varying periods of constipation, from a couple of days to 10 to 12 days. I was left feeling lethargic, bloated uncomfortable and varying degrees of pain

After Dr Fraser sent his letter with the suggested treatment, I received a call from the practice to collect my prescription

Nothing springs to mind.

Fine thank you, I do better on a reduced dairy and wheat diet.  If that has not been managed, I will experience a couple of days constipation and bloating, however once adjusted everything settles down to a regular pattern.

Patient story 2:

VICKI IS A 74-YEAR OLD FEMALE PATIENT WITH LONG STANDING CONSTIPATION. HER HYDROGEN AND METHANE BREATH TEST SHOWED A BASELINE METHANE READING OF 36 PARTS PER MILLION (PPM) WHICH ROSE TO 132PPM DURING THE TEST– NORMAL IS <10PPM

Except for six weeks of runny bowels, about a year ago after I came back from a cruise, I only remember being constipated. As having runny bowels was so unusual I went to the GP who sent me for a colonoscopy - the reason why I initially consulted Dr Chris Fraser.

I have a feeling that I may have been constipated as a child. I remember the embarrassment of passing wind in church and hoping no-one would know it was me.

The constipation really set in when I was given a huge dose of antidepressants after the birth of my first child at the age of 21. I was prescribed three of the 25mg yellow pills of amitriptyline three times a day. I took these for about 12 years. There was never a review. I did try once to stop taking them but felt terrible. During the 12 or so years when I was on the high dose of amitriptyline I was horribly constipated. Every 7 days or so I would take Senacot until I had diarrhoea.

I think it must have caused my bowels to stop working properly. Even when I stopped taking amitriptyline, I had to take laxatives quite often to open my bowels. When I started lecturing I was so nervous that those mornings I would usually have a bowel movement without laxatives

Constipation and the resulting smelly wind was a terrible social problem for me and it also affected my sexual relationships.

About 25 years ago, when I met my second husband, who is a psychiatrist, he suggested that I have oat-bran for breakfast every morning. For quite a long time this worked to stop me being so constipated. Then, about seven years ago, I developed burning pains in my feet. It must have happened slowly over the period before. It was so bad that it affected my sleeping and that made everything difficult. I went to see a neurologist who diagnosed peripheral neuropathy and suggested that I take amitriptyline at night. I resisted this for quite a long time, because of my previous experience with amitriptyline, but not sleeping was having such a bad effect on me that I decided to try it. I’ve taken 20mg of amitriptyline for about 5 years now. It works to make me sleep but of course has the effect of making my constipation worse. When I saw Chris Fraser I’d got to a stage where I didn’t have a bowel movement without taking laxatives.

Dr Chris Fraser prescribed the antibiotics and wrote a private prescription for me. The chemist questioned it and had to ring Dr Fraser to check that it was OK.

I felt fine. I’m not aware that I had any side-effects.

I am feeling much happier. I’m still on the constipated side and still have some wind, though not so smelly as sometimes before. Initially I was still taking one tablet of dulcolax every few days to produce a bowel movement. However, because wheat gluten didn’t seem to be having such a bad effect on my gut, I have replaced my usual breakfast of a bowel of oat bran porridge with a bowel of all-bran (with fruit and yoghurt) for breakfast for the last six weeks During that time I haven’t needed to take any laxatives. I’ve had bowel movements every day, sometimes twice a day. The faeces are on the hard side and I find it quite difficult to empty my lower bowel completely - which may account for the wind. But it’s nothing like as bad as it was. I don’t feel depressed about it anymore. I’m going to try taking probiotics and I feel reassured by Chris Fraser’s suggestion that if the All-bran stops working I could try one of the newer kinds of everyday laxatives and even repeat the anti-biotic treatment. 

Patient story 3:

DAVID  IS A 28-YEAR OLD MALE PATIENT WITH LONG STANDING CONSTIPATION. 

My symptoms started about 5 years ago

I had a lot less control of my bowel, which would greatly limit where and when I could do things. If I needed to 'go', I needed to immediately.

I had to limit my diet and meant I cut down on white bread, white rice, pasta, fruits and vegetables, alcohol and caffeine - basically I had a very plain diet.

If I ate something that didn't agree, it'd be very uncomfortable for a few days, limited my sleep, which then affected my moods. 

I was given a private prescription from Dr Anthony Hobson at FGC, which gave me a ten-day supply. (I'm pretty sure I was given Metronidazole and Ciprofloxacin).

No side effects.

The treatment of SIBO has made my life much better and happier. I'm back to eating the vast majority of food and drink (I still need to be careful with caffeine, alcohol and spicy foods, but I can at least enjoy them again). I take less IBS medication and I'm generally a lot happier. So thank you!

Conclusion

A happy gut contains a thriving community of microorganisms, which together make up the microbiome. An imbalance in this diverse microbiome, such as an increase in methane-producing bacteria, can have a direct impact on gastrointestinal health and result in unpleasant symptoms of bloating and constipation.

The most prolific methane producer in the gut is Methanobrevibacter smithii - making up 94% of all methane-producing species in humans. Oxygen is toxic to M.smithii, meaning it undergoes anaerobic respiration, a process which produces methane. Studies have shown patients with more severe constipation have higher levels of methane, and symptoms can be relieved by reducing levels of methane, confirming the relationship between methane levels and gut symptoms. While M.smithii is a common culprit of methane production, it can also be caused by small intestinal bacterial overgrowth (SIBO). In SIBO patients there is an abnormal amount of bacteria in the small bowel, associated with several common gut disorders such as Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (IBD), and coeliac disease.


Excess methane, and consequent constipation, is treated most effectively with a combination of rifaximin and neomycin. Clinical trial data showed that a combination of rifaximin and neomycin reduced intestinal methane levels by up to 90%.  These antibiotics are not absorbed by the body so they act specifically in the gut. Unlike some antibiotics, they do not eradicate the entire microbiome – preserving the good bacteria to restore balance in the gut community.

A new synthetic drug, SYN-010, is being developed in the US for the treatment of constipation-predominant IBS. This drug is adapted from statins, typically used to lower cholesterol, scientists discovered they also prevent M. smithii growth, therefore reducing methane production without affecting the microbiome.  

A simple hydrogen/methane breath test is all that is required to determine if your constipation is caused by an overproduction of methane. Methane produced in the gut diffuses into the bloodstream and can be expelled by the lungs as breath, allowing the levels to be measured in a non-invasive way. Results can be analysed quickly, allowing for an appropriate treatment plan to be implemented to effectively relieve your symptoms.

For more information on Dr Chris Fraser, Consultant Gastroenterologist at The Royal Infirmary of Edinburgh, Spire Edinburgh Hospitals and The Edinburgh Clinic Scotland - please visit: www.drchrisfraser.com

For more information on The Functional Gut Clinic or for any other enquires please call 0161 302 7777

 (Mon-Friday 9am-5pm)

www.TheFunctionalGutClinic.com 



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