Dr. Weyrich's Naturopathic Functional Medicine Notebook is a collection of information on topics of interest to Dr. Weyrich that may be of interest to the world wide audience. Due to limitations of time, not all information that Dr. Weyrich knows or would like to further research is published here. Dr. Weyrich welcomes financial contributions to support specific research topics, as well as copies of non-free access journal articles for him to review on a topic. Constructive criticism is also welcome.


Overview of Dysbiosis and SIBO

The gastrointestinal tract normally contains many different species of microorganisms (bacteria, yeasts, fungi) living in a mutually competitive and symbiotic fashion. Some of these microorganisms are considered to be beneficial - they aid in digestion, manufacture vitamins, and perhaps most importantly keep harmful microorganisms in check.

Dysbiosis occurs when the balance is disturbed and beneficial microorganisms become overgrown by harmful microorganisms (bacteria, yeasts, fungi, and parasites). Often this can be due to oral antibiotics killing beneficial bacteria.

Go to SIBO SIBO is a special case of intestinal dysbiosis that is characterized by an overgrowth of bacteria in the small intestines.

Complimentary and alternative treatments for dysbiosis that are considered below include:

  • Low Dose Naltrexone

Etiology of Dysbiosis and SIBO

  • Excessive carbohydrates in diet.
  • Oral antibiotics may kill beneficial bacteria allowing an overgrowth of yeasts and fungi. [Berg1981], [Guentzel1982], [Kennedy1983], [Danna1991], [Ostfeld1977], [Kinsman1989], [vanDerWaaij1987], [Samonis1993], [Samonis1994a], [Samonis1994b], [Kasckin1974], [Shepherd1985].
  • Oral antibiotics may kill beneficial bacteria, allowing an overgrowth of anaerobic bacteria such as Clostridium spp.
  • Antacids or other causes of hypochlorhydria may lower the body's defenses against ingested pathogenic microbes.
  • Environmental toxins and heavy metals may disrupt normal flora or the immune system's ability to eliminate pathogenic microbes.
  • Pancreatic insufficiency.
  • Low fiber diet, opiate use, enteric nervous system disruption, or other causes of slow bowel transit time.
  • Poor immune function.
  • Adrenal stress and reduction in secretory IgA production.
  • Other pathogenic microbes include E. coli, Salmonella, Giardia, Blastocystis, Cryptosporidium, and yeasts.

Diagnosis of Dysbiosis and SIBO

  • Hydrogen/Methane breath test for Go to SIBO SIBO.
  • Chiropractic, Naturopathic, or Osteopathic evaluation of the spine for possible nerve irritation due to subluxation.
  • Digestive Stool Analysis to characterize contributory microorganisms and general gut health.
  • Acute abdominal pain requires emergency evaluation; chronic abdominal pain should include upper and/or lower GI tract endoscopy and possibly CAT scan.

Differential Diagnosis of Dysbiosis and SIBO

  • Acute abdominal pain requires emergency evaluation to rule out appendicitis and other emergent conditions; chronic abdominal pain should include upper and/or lower GI tract endoscopy and possibly CAT scan.

Treatment of Dysbiosis and SIBO

SIBO

Treatment of SIBO has been reviewed Go to here here. Note that this treatment focuses on carbohydrate restriction and antibiotic treatment of bacterial overgrowth, and does not consider possible concomitant yeast/fungal dysbiosis, and does not include treatments to heal the inflamed tissue (other than removing the cause).

Prokinetic agents including Low Dose Naltrexone (LDN) may be helpful.

Yeast

Nystatin is the drug of choice for treating dysbiotic overgrowths of yeast and fungi in the gastrointestinal tract [Shaw2008]. Beware of the Herxheimer reaction when treating yeast and fungal dysbiosis by either antibiotic or naturopathic means. The rapid kill-off reaction may liberate a large amount of yeast/fungal endotoxins, which may exacerbate the symptoms being treated or even induce additional symptoms of yeast/fungal intoxication for several days. Some authors recommend concomitant use of activated charcoal or bentonite to help absorb these endotoxins [Shaw2008]. Probiotics such as Lactobacillus acidophilus GG and Saccharomyces boulardii are also useful [Shaw2008].

Clostrida

Dysbiotic overgrowths of Clostridia spp. can be treated with the antibiotics vancomycin or metronidazole (Flagyl) and probiotics [GP] (also consider naturopathic treatments). Beware of the Herxheimer reaction when treating Clostridia spp. dysbiosis by either antibiotic or naturopathic means. The rapid kill-off reaction may liberate a large amount of clostridial endotoxins, which may exacerbate the symptoms being treated or even induce additional symptoms of Clostridia spp. intoxication for several days. Some authors recommend concomitant use of activated charcoal or bentonite to help absorb these endotoxins [Shaw2008]. Probiotics such as Lactobacillus acidophilus GG and Saccharomyces boulardii are also useful [Shaw2008].


Sequelae of Dysbiosis and SIBO

  • Nutritional deficiencies due to loss of beneficial bacteria that normally aid in digestion and produce vitamins.
  • Short-chain fatty acid deficiency due to loss of beneficial bacteria, which increases risk of colon cancer and colitis.
  • Nutritional deficiencies due to consumption by pathogenic microbes.
  • Inflammation in the gut leading to hyperpermeability (leaky gut).
  • Deconjugation of waste bile acids by pathogenic microbes interferes with liver's elimination of environmental toxins and hormones.

Pathophysiology of Dysbiosis and SIBO

Yeast (Candida, Saccharomyces)

Yeast cells may exist in more than one form [Shaw2008]. The hypha form is a more invasive colony-forming form that invades the lining of the gastrointestinal tract and secretes digestive enzymes that damages the wall of the gastrointestinal tract and possibly protective Immunoglobulin-A (IgA) [Banno1985], [Pugh1975]. This damage may lead to Leaky Gut Syndrome and decreased secretion of the hormone secretin [Shaw2008].

Another form that yeast can take is the cell-wall deficient form [Shaw2008].

Clostridia

The bacteria Clostridium tetani is known to produce a potent neurotoxin that causes rigid paralysis. Individuals with tetanus have extreme sensory sensitivity to light and noise, and have trouble chewing and swallowing, similar to some cases of autism [Shaw2008] [Crone1992], [Ogunyemi1986]. Subacute infections of Clostridium tetani in the gut have been reported [Wells1983].

The bacteria Clostridium botulinum is known to produce a potent neurotoxin that causes flaccid paralysis.

The mechanism of action of Clostridium spp. neurotoxins has been discussed [Montecucco1994] and it has been pointed out that the structural gene for the Clostridium spp. neurotoxin is located on a plasmid, which allows for transfer of this toxin-producing gene from one species of Clostridium to another [Finn1984]. Furthermore, the toxins produced by Clostridium tetani, Clostridium botulinum, Clostridium barati, and Clostridium butyricum are all very similar [Finn1984].

Many other species of Clostridium are known to contribute to dysbiosis, so it is reasonable to consider the possibility that some of these bacteria might produce neurotoxins capable of producing the symptoms of autism or ADD. Because Clostridium spp. are strict anaerobes, they are very difficult to isolate and culture. Hence they are poorly characterized [Shaw2008].

Antibiotic treatments that tend to promote overgrowth of Clostridium spp. are often observed to worsen the symptoms of autism and ADD, while antibiotic treatments that tend to kill Clostridium spp. are often observed to improve these same symptoms [Sandler2000], [Shaw2008].

According to research by Walter Gattaz and William Shaw, HPHPA, a metabolite derived from Clostridium spp. metabolism is found in unusually high levels in the urine of patients suffering from schizophrenia, autism, and also intestinal overgrowth of Clostridium difficile [Shaw2008]. HPHPA and other metabolites of the metabolism of Clostridium spp. are detectible by the Organic Acid Test.

One possible explanation for the neurotoxicity of Clostridium spp. is their ability to metabolize the essential amino acid phenylalanine via microbial meta-hydroxylation of phenylalanine to form 3-hydroxyphenylalanine (an analog of tyrosine, which is 4-hydroxyphenylalanine), which is then further processed by the human biosynthetic pathways to form 3,5-dihydroxyphenylalanine (an analog of 3,4-dihydroxyphenylalanine, which is also known as the neurotransmitter precursor called DOPA). This DOPA analog is then further metabolized by human biosynthetic pathways to analogs of the neurotransmitters dopamine, norepinephrine, and epinephrine [Shaw2008, pg 14]. Administration of 3-hydroxyphenylalanine (tyrosine analog) to rats has been observed to result in a characteristic behavioral syndrome in rats consisting of forepaw padding, head weaving, backwards walking, splayed hind limbs, wet dog shakes, hyperactivity and hyperreactivity, as well as depletion of the catecholamine neurotransmitters in the brain and elevation of the dopamine analog (homovanillic acid, HVA) in the urine [Dyck1982], [Shaw2008].

Another possible explanation for the neurotoxicity of Clostridium spp. is their ability to deaminate the essential amino acid phenylalanine to form phenylpropionic acid, which is an inhibitor of the enzymes in the brain that metabolize endogenous opioids such as enkephalins and endorphins [Giusti1985], [Blum1987].

It has also been hypothesized [Shaw2008] that some metabolite of Clostridium spp. may interfere with the normal conversion of dopamine to norepinephine and epinephrine, based on the observation that the ratio of the dopamine analog metabolite homovanillic acid (HVA) to the norepinephrine/epinephrine metabolite vanillylmandelic acid (VMA) is elevated in the organic acid test when HPHPA is elevated. Blocking the normal conversion of dopamine into norepinephrine would result in a build-up of excess dopamine, which is associated with the hyperactivity and stereotypical behaviors as are found in autism. Note that drugs such as phenothiazines and haloperidol, which are used to treat autism, block the dopamine receptor [Shaw2008].

Caution may be indicated in the use of phenylalanine supplementation in the presence of Clostridium spp. dysbiosis, as this may result in an exacerbation of the build-up of dopamine [Shaw2008].

Clostridium spp. are spore-forming bacteria, which means that under adverse conditions, e.g. antibiotic therapy, they can encase themselves in a hard shell and go to sleep until more suitable conditions return. Thus it is not unusual to experience a relapse after removal of antibiotic therapy. The addition of probiotics (beneficial bacteria that competitively suppress Clostridium spp.) is a useful adjunct to antibiotic therapy [Gorbach1987]. While the probiotic Lactobacillus acidophilus GG is reported to give good results, other probiotics are reported to be less useful [Shaw2008].


Hypotheses regarding Dysbiosis and SIBO

Teresa Binstock has hypothesized that dysbiosis early in life induced by early use of antibiotics may interfere with the child's development of immune discernment between normal flora versus pathogenic yeasts and bacteria. It is observed that under normal circumstances secretory IgA does not react with normal flora. It is not clear how the body learns to recognize normal flora as non-pathogenic, but CD5+ B-cells have been suggested to have a role [Shaw2008]. Dr. Weyrich notes that B and T cells that are reactive to self (and presumably normal flora) are actually killed off during maturation of the immune system, leaving only cells reactive to non-self.


References for Dysbiosis and SIBO