Showing posts with label hypothyroidism. Show all posts
Showing posts with label hypothyroidism. Show all posts

Finding The Root Of All Evil

It can be a difficult and extremely frustrating process finding the cause of your many, varied and seemingly unconnected symptoms.  And it will take time, some curiosity, objectivity and some serious cash.  Tests.  Tests cost money, appointments cost money, data costs money, time off work costs money (opportunity cost at least for you economists).  But without finding the reason you have become unable to adequately digest typical foods there is a good possibility of recurrence, in fact, a probability or certainty of recurrence.

Here's my quick list and I will update this as I come across more possible causes of digestive dysbiosis as I continue my research:
  1. Gallbladder and liver congestion or other issues
  2. Colon congestion
  3. Hypochlorhydria (more likely a consequence rather than a cause)
  4. Leaky Gut (for our purposes this can be a "cause" but it has its own causes we will explore)
  5. Celiac disease
  6. Hypothyroidism
  7. Chronic diarrhea
  8. Candidiasis (possibly a consequence rather than a cause)
  9. Colitis (possibly a consequence rather than a cause)
  10. Excessive and/or long term anti-biotic use
  11. Diverticulitis (possibly a consequence)
  12. Cancer   
  13. An episode of serious/extended digestive upset (dysentery, e coli, salmonella, giardiasis, etc)
Keep in mind I'm looking for cold, hard causes - not symptoms or consequences of dysbiosis.  CAUSES.  This is what your gastroenterologist is looking for when he innocently (or not so innocently) recommends for the millionth time that you get a colonoscopy/endoscopy (double).  CAUSES.  More often that not he doesn't find anything and then refers you to a nutritionist or dietitian since he claims he can no longer help you.  OH how many times I've heard this sad, painful, frustrating story.  How many deductibles have been wasted on endoscopies?  Not to mention the prep will throw you off for a week and you'll have to take 1+ day off of work.  

But that's the least of your worries.  You need an enemy you can stare down and focus your ever-dwindling financial resources on destroying.  Fortunately, all the causes I note above can be confirmed or denied with the following tests:
  • HIDC for gallbladder function
  • Endoscopy/colonoscopy for celiac, colitis and diverticulitis (also CT Scan for diverticulitis)
  • Genova Diagnostics GI Effects Microbial Ecology Profile for #5, #8, #11, #6
  • Genova Diagnostics Nutreval will help you find your deficiencies
  • Saliva analysis will be helpful in determining any adrenal insufficiencis or need for DHEA supplementation which is quite common in chronic fatigue-related health problems
  • Blood test for hypothyroidism
That's not that bad for finding the root cause(s) of your misery.  The challenge will be creating a plan once you find the root cause of your digestive dysfunction.  Most likely your plan will include multiple steps as you've probably screwed up multiple cycles in the process of living through months if not years of dysbiosis and malabsorption.  For example, if you have hypochlorhydria that means you probably have SIBO, food intolerances, chronic diarrhea, insomnia, chronic fatigue, foggy thinking, memory issues, hypothyroidsim and even gallbladder issues and liver congestion issues.  If you're walking you probably don't have acute liver issues since this is one of the most important organs in your body.  Much to say, you'll have to attack each of those issues in a specific order until you can finally rid yourself of SIBO and your other symptoms by antibiotic or any effective means.

If I had to put ONE CAUSE at the top of the pyramid, well, I couldn't do it.  But I could put TWO CAUSES at the top of the list:  Thyroid/Adrenal Issues and Leaky Gut.  If I could put THREE CAUSES all at the top of importance list it would be:  Thyroid/Adrenal Issues, Episode of Extended Digestive Upset and Leaky Gut.  If you take care of these, you will find that nearly all of your other symptoms will fall away (perhaps very slowly) by default.  Until you take care of these three you will not heal.  It is simply impossible to heal with these conditions lingering on in your body.  In order:  address your thyroid, address your adrenal issues, address your leaky gut.  When you have done all these to your gut's satisfaction, your symptoms will either vanish or be 95% eliminated.

Let's address them one by one...

The liver and gallbladder are closely related.  For our purposes, the liver produces bile and stores it in the gallbladder.  The liver and gallbladder release the bile into the small intestine especially when fatty foods are eaten and this bile serves to enable digestion and absorption of nutrition as well as regulate bacteria and any sort of intruders such as parasites, viruses and pathogenic bacteria.  For most of us, pathogenic bacteria are not the problem but bacteria are not well regulated when bile is not healthy or free-flowing and abundant.  That's why typically the types of bacteria that overgrow are not pathogenic and therefore our body's immune response to that bacteria is confused at best.  For example, Streptococcus and non-pathogenic E Coli. can overgrow and these strains are found in the nasal, oral, esophageal and intestinal tracts.  So why would your immune system have an easy time regulating these strains when they are already typically present and have been all your life?

On an American diet which pays no attention to balance or food/liquid combinations and highly values fat, carbs and sugar the liver and gallbladder do not thrive.  In fact, the American diet is just about the worst possible situation you can consistently throw your liver into.  For some people, their liver finds a way and in the absence of any sort of upsetting event (giardia, dysentery, extended pathogenic infection, extended use of antibiotics, extended diarhhea, etc) things generally work out.  I am not one of those people.  I traveled abroad in high school and ended up with giardia on extended anti-biotics, never quite got better and continued to have daily diarhhea for 12 years before food intolerances and dysbiosis fully set in.  That is exactly when I hit the books and dedicated most of my free time to uncovering the mysteries of a screwed up digestive system.

The liver/gallbladder needs to be flushed, cleaned and healed.  See here for more info on how to do this.  Initially this process takes about 2 months and after that just minimal maintenance is needed.  Bile can coagulate and form soft or hard stones that get lodged in both your liver and gallbladder.  If this coagulated bile stays there long enough it can start to become toxic and even get infected.  When it gets toxic, you start releasing toxic bile into your small intestine which further irritates the lining of your gut, does not adequately do its job of aiding digestion or regulate bacteria and parasites.  Can you see the many vicious cycles forming as we address more and more gut issues?  Unless you flush and cleanse and heal your liver/gallbladder you will be continuing to release toxic bile into your intestines and further contributing to dysfunction and dysbiosis.  

You'll soon see (if you haven't already) that there are no shortcuts with your body.  Under the right conditions, given adequate time, your body will heal itself.  Without the right conditions and the right amount of time, your body will not heal itself and will be driven further into dysfunction whether that process is slow or fast.  If I could sum up this blog in one idea it would be the exploration of the details surrounding the conditions in which your body will heal itself.  This is the central question.  Why do all this?  Life to the full.  That's why.          

The colon can build up residue and impacted fecal matter on its walls.  This can also happen on the walls of the small intestine.  This is a breeding ground for unwanted bacteria and parasites and since you do your absorbing of nutrition through the walls of the intestines, when they are blocked then obviously this inhibits absorption.  This further contributes to dysfunction.  Your colon will not cleanse itself to the extent that we're looking for and the liver doesn't have a chance if your colon is not cleansed first.  See here for more info on how to go about this.  This will only take about 10 days but requires 5 days of fasting which I was not able to do so I just did the colon cleanse during a liquid diet and separated my liquid food intake from the herbal cleanse intake by an hour or so and this seemed to work fine.  This way, I still managed 1300 calories per day while colon cleansing.  You may be surprised what comes out of you, or if you're not the sifting-through-your-own-feces type then you can simply trust that what you're doing is greatly aiding your cause.  

Leaky gut is perhaps the most pernicious enemy in this whole ordeal.  You've taken care of the colon.  Wonderful.  You're taken care of the liver/gallbladder combo.  Great.  Leaky gut may haunt the remainder of your recovery and will be the responsible party for setbacks, unexpected issues, random blow-ups.  The problem with this entire digestive set-up is that you can't see any of the activity that is going on in your gut.  The only thing you have to go on is other folks' experience, logic, a bit of science/nutrition and this inner intangible "feel good" barometer that, when properly calibrated, tells you when something is helping or hurting your healing process.  Leaky gut refers to the propensity of your small intestine in particular to become perforated as the result of the dysbiosis, toxic bile, bacterial imbalance and parasites that find themselves deep-seated in your small intestine's ecosystem.  When its perforated, your body responds with hypochlorhydria which further disables you from being able to digest your food fully.  The perforations will also allow undigested food particles (cue gluten and other allergens) to enter your blood stream directly which tips off your immune system to react and label these allergens as intruders.  Thus, you begin to react to things like wheat, gluten, onions, eggs, soy, lactose, anything really.  Fortunately, these food intolerances are not allergies and can be dealt with simply by addressing the situation and creating conditions that allow the leaky gut to heal.

Again we focus on creating a situation in which your body can heal itself.  The elements involved with healing the leaky gut include:

  • colon cleanse, liver cleanse, parasite cleanse
  • giving your system a rest by going on a liquids only diet for 1-2 weeks
  • eliminating ALL allergens while still nourishing your body adequately
  • listening to your gut and slowly only adding simple foods you can digest fully
  • incorporating fermented foods (veggies, yoghurt) into each meal 
  • beef marrow bone broth with copious amounts of glutamine morning and evening
  • rest, stretching, breathing, general stress reduction (these attempt to enable general bodily healing)          
Give your body enough time under these conditions and you will heal.  If you don't, something else is still lingering at the root of your digestive dysfunction.

Your quest is a quest to feel as AMAZING as you possibly can.  That makes it sound nice doesn't it?  This quest may cost a lot of money, this quest may make you lose A LOT of weight, this quest may bring you to funny places where you are eating very funny things but this quest must be undertaken inasmuch as your body requires for your healing.  In other words, you are not the decider of what it will take for your gut to heal.  You are NOT in control of this.  Sorry.  Your gut is in the driver's seat.  If it heals in a few months, wonderful.  If it takes years then it takes years, but if you do not delve as deep as is required into the quest you will not be giving your body the conditions it needs to heal itself.

My quest has included a month of a liquid diet that cost me $12000+/year, multiple attempts and failures with various supplements, too many setbacks to count, extended periods of refusing to admit that my diet was not restrictive enough, months of worrying about my low weight and therefore hesitating to take the extreme measures required to cleanse my colon and liver.  OH how I wish it was easier to heal my gut but it's just not.  I had to say goodbye to eating at restaurants for 4 years straight.  I had to say goodbye to scrambled eggs at one point.  I had to say goodbye ANY kind of processed food for 4+ years.  I had to say goodbye to "convenience" and "easy."  Why?  Because it's what my gut required in order to heal.  Your gut does not lie to you.  It needs what it needs.  It won't negotiate, it is not open to discussion.

In summary, do everything you can to find the CAUSE of your chronic and recurring digestive issues because there is one...or ten...somewhere...hiding.  Once you find the causes then create and constantly update and revise your plan for creating the conditions your body needs in order to heal itself.     

Association Between Hypothyroidism and Small Intestinal Bacterial Overgrowth (SIBO)


This is a very helpful paper discussing the connections between SIBO and Hypothyroidism taken from http://jcem.endojournals.org/content/92/11/4180.full. 

Objectives: Small intestinal bacterial overgrowth is defined as an abnormally high bacterial population level in the small intestine. Intestinal motor dysfunction associated with hypothyroidism could predispose to bacterial overgrowth. Luminal bacteria could modulate gastrointestinal symptoms and interfere with levothyroxine absorption. The aims of the present study were to assess the prevalence and clinical pattern of bacterial overgrowth in patients with a history of overt hypothyroidism and the effects of bacterial overgrowth decontamination on thyroid hormone levels.
Methods: A total of 50 consecutive patients with a history of overt hypothyroidism due to autoimmune thyroiditis was enrolled. Diagnosis of bacterial overgrowth was based on positivity to a hydrogen glucose breath test. Bacterial overgrowth positive patients were treated with 1200 mg rifaximin each day for a week. A glucose breath test, gastrointestinal symptoms, and thyroid hormone plasma levels were reassessed 1 month after treatment.
Results: A total of 27 patients with a history of hypothyroidism demonstrated a positive result to the breath test (27 of 50, 54%), compared with two in the control group (two of 40, 5%). The difference was statistically significant (P < 0.001). Abdominal discomfort, flatulence, and bloating were significantly more prevalent in the bacterial overgrowth positive group. These symptoms significantly improved after antibiotic decontamination. Thyroid hormone plasma levels were not significantly affected by successful bacterial overgrowth decontamination.
Conclusions: The history of overt hypothyroidism is associated with bacterial overgrowth development. Excess bacteria could influence clinical gastrointestinal manifestations. Bacterial overgrowth decontamination is associated with improved gastrointestinal symptoms. However, fermenting carbohydrate luminal bacteria do not interfere with thyroid hormone levels.
SMALL INTESTINAL bacterial overgrowth (SIBO) is a clinical condition, caused by an increased level of microorganisms exceeding the presence of more than 106 colony forming units/ml intestinal aspirate or colonic-type bacteria within the small intestine (1).
SIBO is considered a malabsorption syndrome because bacteria can adhere and damage small bowel absorptive surface, and can metabolize carbohydrates, lipids, and proteins normally absorbed in the small bowel (2). Although asymptomatic cases exist, SIBO is clinically characterized by signs and symptoms such as abdominal pain, bloating, flatulence, diarrhea, and weight loss (3).
Antibiotic therapy is the cornerstone of the treatment of SIBO. Several absorbable and nonabsorbable broad-spectrum antibiotics can be used. Rifaximin is a rifamycin derivative with antibacterial activity caused by the inhibition of bacterial synthesis of RNA (4). It is active against gram-positive and gram-negative bacteria, including both aerobes and anaerobes (5). Rifaximin 1200 mg/d is an effective treatment to achieve SIBO decontamination without increasing the incidence of side effects (6).
In the healthy subject, the main mechanisms restricting the bacterial colonization in the upper gut are the gastric acid barrier, mucosal and systemic immunity, and intestinal clearance. When these mechanisms fail, bacterial overgrowth develops. Failure of the gastric acid barrier can be caused by Helicobacter pylori-induced gastritis, drug-induced inhibition of acid secretion, autoimmune disease, malnutrition, and aging (7). Regarding local mucosal and systemic immunity, conditions such as HIV or immunoglobulin deficiencies (IgA deficit) can be linked to SIBO development.
Failure of intestinal clearance can be associated with anatomical abnormalities, such as gastrointestinal surgery, intestinal diverticula or fistula, or with conditions that impair intestinal peristalsis, such as myopathic, neuropathic, autoimmune, inflammatory, metabolic, and endocrine diseases (7).
With regard to endocrine disorders, it is known that thyroid hormones may influence gut motility modulating neurological and smooth muscle function (89). Several studies have shown that hypothyroidism could be associated with decreased frequency of rhythmic colonic activity and slower oro-cecal transit time both in animal (10) and human subjects (11).
These neuromuscular disorders are responsible for diarrhea and constipation observed in patients affected by hyperthyroidism and hypothyroidism, respectively (1213).
Patients with hypothyroidism are supplemented with synthetic T4 hormone (levothyroxine-LT4) in oral doses to achieve physiological thyroid hormone serum levels. Many causes of LT4 malabsorption are known and discussed in literature (14). Common causes are gastrointestinal diseases (151617) and infections (18), pancreatic and liver diseases (19), gastrointestinal surgical procedures (2021), dietary interactions (22), drugs (2324), and pregnancy (25). However, causes of malabsorption are sometimes unknown, and increased doses of T4 are needed for hypothyroidism treatment.
Aims of the present study are to assess: 1) whether a history of overt hypothyroidism is associated with SIBO development, 2) the clinical manifestation of SIBO and the effects of SIBO decontamination in patients with a history of overt hypothyroidism, and 3) whether the presence of SIBO affects thyroid hormone levels.

Patients and Methods

The study was conducted between September 2005 and July 2006 on consecutive outpatients from the Gastroenterology, Endocrinology, and Internal Medicine Departments of the Gemelli Hospital, Catholic University of Rome.

Eligibility criteria

Patients with a history of overt hypothyroidism due to autoimmune thyroiditis were enrolled. The diagnosis was based on standard biochemical and instrumental criteria, which included a biochemical assay of venous blood for thyroid hormones, autoantibodies to thyroid antigens (thyroid peroxidase antibody, antithyroglobulin antibody), and thyroid ultrasound (2627). Serum thyroid hormones and thyroid autoantibodies were determined by commercial kits (Roche Elecsys 1010/2010 and Modular Analytics E170 analyzers; Roche Diagnostics, Indianapolis, IN). Free T3, free T4, and TSH were determined by immunochemiluminescence assay (normal range 2.3–4.2 pg/ml, 8.5–15.5 pg/ml, and 0.35–2.80 μUI/ml, respectively), and thyroid peroxidase antibody and antithyroglobulin antibody were determined by immunofluorescence assay (normal range < 20.0 U/ml and < 80.0 U/ml, respectively).
Diagnosis of overt hypothyroidism was based on serum TSH levels above 2.8 μUI/ml, and free T3and T4 decreased. Autoimmune origins of hypothyroidism were defined by the presence of thyroid autoantibodies and typical thyroid ultrasound signs, such as reduced echogenicity (2627).
All patients were supplemented with synthetic T4 hormone in oral doses, and they achieved euthyroid condition in the 2–6 months before enrolment.
All patients included in the study gave written informed consent.
The exclusion criteria were: age younger than 18 yr; other causes of hypothyroidism; use of antimicrobial agents within the previous 3 months; hypersensitivity to the antibiotics; pregnancy or breast-feeding; clinical conditions predisposing to SIBO; and evidence of major concomitant diseases, including tumors and hepatic and/or renal insufficiency.
All patients were instructed to maintain their usual diet and oral dose of T4, and to avoid prokinetics, other antibiotics, and drugs interfering with intestinal motility during the study period.
For each patient, age at hypothyroidism diagnosis, time from diagnosis, and median daily dose of T4 were recorded.
The control group consisted of healthy subjects, without a history and clinical evidence of thyroid disease and without any well-known clinical conditions predisposing them to SIBO. They were enrolled among the medical staff of our hospital, and were of similar sex and age.
All participants in the study came from Rome and the surrounding area.

Breath hydrogen (H2) testing

Glucose breath test (GBT) was performed under standard conditions. In the 30 d preceding the test, no patients received antibiotics or laxatives. To minimize basal H2 excretion, subjects were asked to have a carbohydrate-restricted dinner on the day before the test and to fast for at least 12 h. On the day of testing, patients did a mouthwash with 20 ml chlorhexidine 0.05%. Smoking and physical exercise were not allowed for 30 min before and during the test. End-alveolar breath samples were collected immediately before glucose ingestion. A dose of 50 g glucose in the form of iso-osmotic solution was then administered, and samples were taken every 10 min for 2 h, respectively using a two-bag system. The two-bag system is a device consisting of a mouthpiece, a T valve, and two collapsible bags; the first one collects dead space air, and the second one collects alveolar air. From this bag the breath sample was aspirated into a 20-ml plastic syringe. Samples were analyzed immediately using a model Quintron Gas Chromatograph (Quintron Instrument Co., Milwaukee, WI).
The test was considered as indicative of the presence of SIBO when the peak, i.e. the increase over the baseline of H2 levels, was more than 12 parts per million (28).
The reproducibility of GBTs in our laboratory in patient populations (n = 20) is good, with a κ-statistic of 0.88 and 95% agreement on tests performed 1 wk apart.

Antibiotic treatment

All patients affected by SIBO received rifaximin (Normix 200 mg tablets; Alfa-Wassermann, Woerden, The Netherlands) 1200 mg/d (two tablets three times a day) for 7 d.
A GBT was repeated 1 month after the end of therapy in all treated patients to assess SIBO eradication.

Laboratory parameters

The main hematochemical parameters (total blood cell count, glucose, blood urea nitrogen, creatinine, electrolytes, total protein, albumin, bilirubin, aspartate aminotransferase, alanine aminotransferase, c-glutamyl-transpeptidase, alkaline phosphate, and prothrombin time) were evaluated in all patients at enrolment and 3 d after the end of the antibiotic treatment in patients affected by SIBO.
Thyroid hormone levels were assessed in all patients at enrolment, and 1 month after the end of the antibiotic treatment in patients affected by SIBO and 1 month after the first evaluation in patients without SIBO.

Symptoms assessment

Each patient was asked to complete a questionnaire using a four-point Likert scale (0 = absence, 1 = mild, 2 = moderate, and 3 = severe), including classic gastrointestinal symptoms (abdominal discomfort/pain, bloating, flatulence, constipation, and diarrhea), at enrollment. All symptoms were reevaluated after antibiotic treatment.
“Adverse experiences” occurring during the treatment period were recorded on daily diary cards, with the following grades: 1, mild; 2, moderate; and 3, severe (13). Patient compliance was assessed by a pill count of the drugs boxes returned the day after the last day of therapy administration. Low compliance was defined as more than 20% of pills returned. Side effects were defined as the occurrence of: 1) abnormalities in the main hematochemical parameters considered; and 2) “adverse experiences,” considered as clinical findings or patient complaints that were not present in the 24 h immediately before enrollment in the trial.

Data analysis

To detect differences in SIBO prevalence, the χ2 test was used. Differences according to age at hypothyroidism diagnosis, time from diagnosis, and median daily dose of T4 between hypothyroid patients with or without SIBO were evaluated by the Levene test. To detect gastrointestinal symptoms, we used a four-point Likert scale (0 = absence, 1 = mild, 2 = moderate, and 3 = severe), but for the purpose of statistical analysis, the prevalence of gastrointestinal symptoms was considered as a binomial variable (1–3 = present/0 = absent). Differences were evaluated by the χ2 or Fisher exact test, as appropriate. Differences in thyroid hormone levels before and after antibiotic treatment were evaluated by the Student’s t test. The statistical analysis was performed using Stata 6.0 (StataCorp, College Station, TX). A P value less than 0.05 was considered significant.

Results

Patients characteristics

A total of 50 patients with hypothyroidism and 40 controls were enrolled. Characteristics of the study groups are summarized in Table 1.
View this table:
TABLE 1.
Demographic and clinical characteristics of patients with a history of hypothyroidism and control group

GBT positivity in patients and controls

In the patients’ group, 27 subjects were found to be positive to GBT (27 of 50, 54%) compared with two in the control group (two of 40, 5%). The difference between groups was statistically significant (P < 0.001; odds ratio 22.3, 95% confidence interval 4.8–102.7; Fig. 1).
FIG. 1.
SIBO prevalence in patients with a history of hypothyroidism (group A) vs. control group (group B). *, P < 0.001.

Clinical parameters of hypothyroidism and SIBO

No significant association was found between the presence of SIBO and age at hypothyroidism diagnosis, time from diagnosis, and median T4 daily dose (Table 2).
View this table:
TABLE 2.
Age at hypothyroidism diagnosis, time from diagnosis, and median T4 daily dose in patients with and without SIBO

Gastrointestinal symptoms in SIBO-positive and SIBO-negative patients

The prevalence of SIBO-related gastrointestinal symptoms in patients with a history of hypothyroidism are reported in Table 3. Abdominal discomfort, bloating, and flatulence were significantly associated with SIBO (P < 0.01). There was no statistically significant correlation between SIBO positivity and bowel habit (constipation or diarrhea).
View this table:
TABLE 3.
Prevalence of gastrointestinal symptoms (%) in patients with a history of hypothyroidism affected by SIBO (group 1) vs. patients with history of hypothyroidism without SIBO (group 2)

Decontamination rate and side effects profile

The GBT decontamination rate in SIBO patients was 70.4% (19 of 27) after a 1-wk course with rifaximin 1200 mg/d. No dropouts were recorded.
No abnormalities in the tested laboratory parameters (total blood cell count, liver and kidney function) were observed at the control performed 3 d after the end of the treatment.
Compliance with rifaximin was excellent. More than 95% of patients in all groups took the prescribed number of tablets for the 7-d treatment. The prevalence of adverse events was very low: one patient complained of nausea and one of headache. The adverse events reported were both mild and disappeared rapidly after treatment.

Gastrointestinal symptoms and SIBO decontamination

A significant improvement in abdominal discomfort, bloating, and flatulence was observed in the group of patients decontaminated after rifaximin therapy (P < 0.01). No differences were found with regard to constipation and diarrhea after SIBO decontamination (Table 4).
View this table:
TABLE 4.
Prevalence of gastrointestinal symptoms (%) in 19 patients with a history of hypothyroidism affected by SIBO and successfully decontaminated before and after antibiotic treatment
None of the recorded gastrointestinal symptoms significantly improved in the group of treated but nondecontaminated patients (data not shown).

Thyroid hormone levels and SIBO decontamination

Median T4 daily dosage (μg/d; μg/kg) was similar between patients who responded and those who did not respond to the antibiotic treatment (96.54; 1.42 vs. 94.89; 1.34).
No statistically significant difference was observed regarding thyroid hormone levels in the 19 SIBO decontaminated patients before and after antibiotic treatment (Table 5).
View this table:
TABLE 5.
Thyroid hormone plasma levels in patients with a history of hypothyroidism affected by SIBO, eradicated by rifaximin, before and after antibiotic treatment
Thyroid hormone levels were also reassessed in patients without SIBO showing values similar to those of the first evaluation (data not shown).

Discussion

Interdigestive migrating motor complexes play a major role in the clearance of bacteria from the gut (29). In rats, bacterial overgrowth is induced by pharmacological disruption of migrating motor complexes, and restoration of intestinal motility reduces endoluminal bacterial density to normal values (303132). Several diseases characterized by the disruption of normal motor events are often associated with SIBO: scleroderma (33), idiopathic intestinal pseudo-obstruction, autonomic neuropathy, and radiation enteropathy (343536). Thyroid hormones may influence gut motility modulating neurological and smooth muscle function, and hypothyroidism could be associated with decreased frequency of rhythmic colonic activity and slower oro-cecal transit time (1011). Our study shows that a history of overt hypothyroidism is a risk factor for SIBO development. The pathogenic link could be that intestinal motor dysfunction associated with hypothyroidism reduces the ability of the small bowel to clear luminal bacteria. In our study all enrolled patients had a history of overt hypothyroidism. It could be very interesting to evaluate if differences exist between subclinical and overt hypothyroidism concerning association with SIBO. We can speculate that the prevalence of intestinal overgrowth could be related to the severity of hypothyroidism. On the other hand, intestinal motility could be more heavily altered in overt hypothyroid patients developing SIBO. Intestinal myoelectrical activity, oro-cecal transit time, and intestinal neurohormonal regulation should be studied in future trials to confirm this hypothesis, and elucidate pathophysiological mechanisms behind the association between hypothyroidism and SIBO.
In the present study, all patients were under levothyroxine therapy, achieving euthyroidism at enrollment. It is possible that once SIBO is established during the hypothyroid phase, it does not clear spontaneously, even if made euthyroid.
The prevalence of gastrointestinal symptoms such as abdominal discomfort, bloating, and flatulence is significantly higher in SIBO-positive patients compared with SIBO-negative, and decontamination therapy is associated with statistically significant levels of clinical improvement. These findings suggest that, in patients with hypothyroidism, the presence of gastrointestinal symptoms after reaching a euthyroid condition is related to SIBO persistence. It is well known that, in patients affected by chronic functional disorders, gastrointestinal symptoms respond to placebo in 20–50% of cases. However, two recent randomized double-blind placebo-controlled trials by Pimentel (37) and Sharara (38et al. showed that rifaximin significantly improved gastrointestinal symptoms in patients with chronic functional disorders and that symptom improvement was associated with a reduction in H2 breath excretion. In addition, in our study, rifaximin is administered only for a short time, with benefits tested after 1 month; the placebo effect could be minimal after this time.
SIBO-related bacteria excess can also interfere with the absorption of many substances, such as carbohydrates, proteins, and lipids (2). A direct mucosal injury resulting from bacterial adherence and increased production of enterotoxins could affect the activity of brush-border disaccharidases. On the other hand, bacteria can compete with the host for nutrient use (2). In our study the presence of SIBO is not associated with T4 malabsorption, and SIBO decontamination does not modify thyroid hormone levels. Bacterial population contaminating the upper gut is extremely complex, and metabolic functions are very difficult to investigate (39). In the present study, SIBO diagnosis is based on the H2 breath test. Its positivity suggests the presence of sugars fermenting bacteria (40), thus producing H2 and other metabolites. It is possible that this test does not identify bacteria using proteins and amino acids such as T4 as their prevalent energetic substrates. It could explain why SIBO does not interfere with thyroid hormone levels in our study. On the other hand, the high prevalence of symptoms such as bloating and flatulence could reflect a prevalent “fermentative bacteria” in our population.
In conclusion, a history of overt hypothyroidism is associated with SIBO development and persistence. Excessive bacteria could modulate neuromuscular function and influence clinical manifestations. SIBO decontamination is associated with gastrointestinal symptom improvement. Finally, carbohydrate fermenting bacteria do not interfere with thyroid hormone levels.
Further studies are needed to characterize the bacteria species involved in SIBO, and clarify their metabolic functions and their relationship with intestinal motility.