Bacterial Overgrowth

 My Bovine-Like Life with Methane-Making  Gut Germs 

Methane has become very important to me.  In many ways this molecule composed simply of hydrogen and carbon dictates to me my daily life.  It tells me what to eat and how much.  Microrganisms wait patiently in my stomach for me to feed them the carbohydrate they need to produce methane.  The methane then inflates my gut causing bloating and lots of burping.   These methane-producing microorganisms are like Al Qaeda terrorists resting in the hills prepared to strike whenever the opportunity comes.  They are nearly impossible to dislodge from the mountains, hills and valleys of my gut.  I now view them as inscrutable and indomitable.

Bacteria have been known to us since the research of Pasteur and Koch at the turn of the nineteenth century.  However, the importance of another group ofmicro-organisms, the Archaea was unknown until the last few decades.  Indeed, they had been unknown to me during my infectious disease consultation practice in the 1970s & 80s; even though I was ignorant of the Archaea, they were not ignorant of me.

Wikipedia provides this background:  “The word archaea comes from the Ancient Greek ἀρχαῖα, meaning 'ancient things" … For a long time archaea were seen as extremophiles that only exist in extreme habitats such as hot springs and salt lakes. However, by the end of the 20th century, archaea had been identified in non-extreme environments as well. Today they are since the 1970s known to be a large and diverse group of organisms that are widely distributed in nature and are common in all habitats. This new appreciation of the importance and ubiquity of archaea came from using polymerase chain reaction ... This allows the detection and identification of organisms that have not been cultured in the laboratory.”

The microscopic Archaea like bacteria have no nucleus. They have been awarded their own separate domain or kingdom, leading to the recognition three living kingdoms, Archaea, Bacteria and Eukaryocytes.  The Eukaryocytes are us.  The cells of Eukaryocytes have a nucleus and include the life forms we are able see as well as a few micro-organisms.  The microscopic Archaea and Bacteria are known as procaryocytes. They have no nucleus—but enough microbiology.

 Unidentified, and certainly uninvited, they have been living in my gut.  The Archaea and some bacteria are methanogens.  They produce methane by fermentation of ingested carbohydrates and are a large source of human intestinal gas.  In most humans they live mostly in the large intestine, however, in some people they extend from their home territory into the small intestine and the stomach.  Here they have easy and rapid access to the carbohydrates that we are encouraged to eat instead of fats and red meat.

In the upper parts of the gastrointestinal tract the gas these microorganisms make is not easily expelled as it is from the colon and causes distention of the stomach and small bowel.  From the stomach, the gas may be released as eructations—belching.  Clinically this aggregate of symptoms certainly is not unique, but it is consistent with the syndrome of Small Intestinal Bacterial Overgrowth Syndrome.  This is somewhat of a double misnomer since both Bacteria and Archaea, produce the gas, and this may occur not only in the small bowel but also the stomach.  A better name, although unwieldy, is the Gastric and Small Intestinal Bacteria & Archaea Overgrowth Syndrome.

While not free of microrganisms in the natural state, the stomach and upper gut, harbor only transient germs which number in only in the hundreds.  When large numbers invade and conditions allow for them to set up habitation, i.e., to colonize, with their population numbers now in the tens of thousands, the effects of their fermentation products are felt.  

Why in some humans do Bacteria and Archeae colonize the upper reaches of the gut with such a large and gaseous population?  Why does his not happen to everyone?  There are two principle actions of the upper gut that keep the potential hordes of microbes in check:  toxic chemicals and sweeping.  This is similar to the work of a German housewife keeping a clean kitchen floor.  The gut’s chemical effect is created by liters of hydrochloric acid that is normally produced daily.  The wildly active acid in the gastric juices is there for a key purpose, to break down meats and other proteins.  As a by-process the acids dissolve the micro-organisms which we unavoidably swallow as well as the germs that may wander from their home in the distal bowel, the colon.  The chemical effective of the gastric acid is aided by the sweeping action, peristalsis, of the alimentary canal.  Well-coordinated peristaltic waves are highly effective in sweeping along food and along with the food, microbes.  The housewife uses her lye and her broom.  We use acid and peristalsis.

In my stomach and small bowel the methanogens have survived in large enough numbers to produce copious amounts of methane.  Enough to make me not only uncomfortable, but regularly sick and impaired from this sickness.  As lamented Job, “Why Me?”  Well, as with many of the ill-fortuned ill, it was of my own doing.  The pump that pushes hydrochloric acid into the stomach was stopped cold by a so-called protein pump inhibitor.  I have taken this type of medication for 20 years after I was found to have an esophageal ulcer from excess acid leaking up from my stomach.  That is another self-induced disease of which you may read in the story of the “Esophageal Ulcer”.

Twenty and more years passed with reduced acidity in my stomach.  More and more I was bothered with eructations and belly distention, and in particular I was distressed after meals.  Such post-prandial discomfort can be the symptom and the sign of truly pernicious conditions, e.g., cancers of the stomach and pancreas among others.  Worried about these, I worried my physicians, and over recent years I had had series of diagnostic tests:  upper endoscopies, CT scans, abdominal ultrasounds examinations and gall-bladder studies.  All had been normal.

The symptoms worsened and started to interfere with my well-regulated life.  One morning I was unable to help with the case discussions with the house staff.  My belly was distended, I was nauseated and felt weak and generally sick, i.e., malaise.  By chance my gastroenterologist was also teaching that Wednesday morning.  As he left the conference, by way of politeness, he asked how I was doing, and unexpectedly for him, I told him.  He immediately said, “You have small bowel overgrowth.”

He arranged for me to have a breath-test.  I drank a solution of  a nonabsorpable sugar, in this case lactulose, my breath was tested for the presence of hydrogen and methane every 20 minutes for 3 hours.  Normally the breath is free of these gases until the sugar reaches the colonic bacteria and archaea; this is a trip that takes about two or three hours.  Large amounts of hydrogen or of methane in the exhaled breath before 2 hours is evidence of bacterial or archaeal colonization upstream from the colon.  Dramatically, at baseline and thereafter my breath contained a large amount of methane.  A second test gave the similar results.  I had methanogens in my stomach and small instestine.  



We now had evidence that methane is the source of my discomfort.  The task now was to reduce the quantity of methanogens and/or to reduce the carbohydrates from which they make the methane.  The first approach has not been successful.  I have taken multiple courses of multiple antimicrobials which has not abated the bloating and belching.  Concurrently I have altered my diet to reduce fermentable carbohydrates. Meats and fats do not  contain carbohydrates, but steady diet of steak while sounding good, shortly becomes tedious and undesirable.  So goes it, and the struggle goes on.

As an after thought, my stomach is similar to the first stomach of the bovine breeds.  Cows have four stomachs, and in the first two these, the rumen and reticulum, the mucosa of the walls are lined with and the lumen is filled with micro-organisms which ferment the fibrous grasses and hay which are the sustenance of cows.
The fermentation products include hydrogen and methane.  Indeed cows are an important source of green house gases and climate change.

I have been joined in my struggle, or perhaps I have joined a struggle.  For decades patients and clinicians have labored over a vague set of signs and symptoms, a syndrome, which include abdominal bloating with discomfort, diarrhea or constipation and more.  Despite much effort and many blind alleys of investigation, this syndrome, known as the Irritable Bowel Syndrome (IBS), continues to plague patients.  In recent years however, IBS has become linked to SIBO since a portion of IBS patients too will have a positive breath test and do respond to oral antimicrobial agents.  

The bloating and eructations are easily explained by the methane in the stomach, but what accounts for the generalized symptoms of malaise and nausea?  It is now recognized that the gut by way of afferent vagal nerve fibers acts something like a second nervous system.  Within the small bowel mucosa, in addition to the usual mucoal cells there are  enterochromaffin cells that produce and secrete neurotransmitters.  This gastrointestinal brain helps coordinate peristalsis, and when these cells are squished by the distention of the gut they give off large amounts hydroxytryptophan which is converted to serotonin.  Serotonin then acts on reflex centers in the brain stem that cause nausea.

Why was the overgrowth of my gut not recognized earlier?  Firstly the hydrogen-breath test although developed years ago was only performed in certain specialized research laboratories.  Now it is more widely available in hospitals and clinics.  Secondly, my symptoms were not disabling until recently and by that time a breath test could be easily obtained.  Importantly my gastroenterologist is young, and had been trained at an academic center with a strong investigational interest in SIBO. He knew about the condition and he knew how to use the test.
Now, 2018, we have diagnosed the cause of my distress but have yet to find a cure.  I go through life belching and bloated.  I am nauseated and regularly use medical cannabis whenever indicated, and I am the judge of that.  Life could be worse!

Thorough

A Thorough Physician

My nearly ninety year-old mother was failing.  She had always been more active than her age-defined cohort, she had cooked, quilted, hooked rugs and was a star personality in the local Presbyterian Church.  She was proud of herself:  her skills, her know-how and her energy.  Now she had become too tired, too fatigued to enjoy these skills.  

Although in part we could attribute her condition to advancing age, her internist, an excellent physician, took our observations earnestly; he was by all standards an earnest man.  She may have not complained to him, but I did, and years before I had been his Chief of Medicine and he my Chief Medical Resident (CMR). Our CMR’s were chosen from among their peers to assist the teaching faculty.  Nearly all CMR’s have been luminary physicians both on the wards and in the clinic.

The physical examination, and the routine focused laboratory examinations were normal:  no anemia, kidney failure, diabetes nor an occult cancer, nor evidence for polymyalgia rheumatica.  The thyroid stimulating hormone level was within the normal range. After this thorough inquiry and examination, he had no explanation for her failure. He was earnestly puzzled

Months passed and repeated evaluations showed no change.  Then he retired and a new physician took his place.  She as he before him had been one of our CMR’s.  

While assisting with the transition of Mother’s care, I told her of the downhill trajectory.  Before Mom was see in her clinic, her new physician had reviewed the medical records, and she found no new data, but she reinterpreted existing data:  although the thyroid stimulating hormone (TSH) level had always measured within the normal range, in the last years it had fallen from a high normal to a low normal level.  

TSH, which comes from the pituitary, the master gland, is lowered by thyroid hormone (TH) which comes from the thyroid gland, and in normal events they act in feedback to each other to balance the levels, much like a teeter-totter.  

Using a graphing function embedded within our new electronic medical record (EMR), she tracked a dramatic steady linear decline in Mother’s TSH.  Her observation that the TSH had persistently fallen meant that the TH had probably risen during that same time to a higher level. TH levels are not routinely measured unless the TSH is in an abnormal range.   In response to the trend of the falling TSH, she measured the TH and it was high.  Mom’s thyroid was overriding the low TSH.  The thyroid gland had become an autonomous force not responding to the signal from the master gland that enough was enough.  

My mother had hyperthyroidism, and additional testing and consultation with an endocrinologist, a thyroid expert, confirmed this.

Mother’s condition is known as Apathetic Hyperthyroidism.  It is unusual, and when it happens it is almost always in old people.  The usual presentation of hyperthyroidism has to do with the TH’s stimulation of the sympathetic nervous system, best know as for the production and release of epinephrine.  This explains why hyperthyroidism usually presents with the tremors of sweaty hands, sleeplessness, and overactive reflexes.  It resembles a case of continuous performance anxiety.   In old people, however, the sympathetic nervous system has usually, to a great degree, withered away, and epinephrine is not abundantly released.  Old patients therefore don’t present with the usual outward signs of the condition, but with manifestations common of old age:  loss of weight, loss of energy and apathy. 

My mother’s highest praise for a doctor was that they had been thorough.  She seemed to reserve this adjective exclusively for physicians.  Both of her physicians had met her approval as thorough, and they were.  Her second physician just happened to synthesize a fresh look at old data using a new tool, the EMR.