Probiotic use for digestive conditions has seen a gradual increase in dosage over the past couple decades. Doses of 7 billion were thought to be very high just ten years ago, while average doses were about 250 million. Today, an average probiotic dose is around 1–5 billion with high-dose probiotics ranging from 30 to 450 billion or more. This increase comes with improvements in the development of probiotics and increased interest in studying high-dose probiotics, as is reflected in the literature.

The gut is home to about 100 trillion bacteria cells—10 times the amount of cells that make up the entire human body. For this reason, high-dose probiotic therapy may have a greater impact on the beneficial modulation of the gut flora, or microbiota. Here I’ll review a few studies on high-dose probiotics for gastrointestinal conditions.

In a randomized, double-blind, placebo-controlled study published in 2010 in the Journal of American Gastroenterology, 225 patients were randomized to one of three groups: two probiotic capsules per day providing 100 billion CFU (colony forming units) of live organisms, one probiotic capsule and one placebo capsule per day providing 50 billion CFU of live organisms, or two placebo capsules.¹ A dose-ranging effect was shown in which the group receiving the 100 billion CFUs had lower incidence of antibiotic-associated diarrhea (AAD) than the 50 billion group, and both probiotic groups had lower incidence versus placebo. In those patients who did acquire AAD, Clostridium difficile-associated diarrhea (CDAD) incidence was lower than the 500 billion CFU group, and both probiotic groups had lower CDAD incidence than placebo.

A previous dose-response study published in 1991 in the journal Microbial Ecology in Health and Disease investigated fecal recovery of the probiotic Lactobacillus casei strain GG (LGG).² In this study, healthy volunteers were assigned to six different groups: 1.5 million, 15 million, 150 million, 1.5 billion, 15 billion and 150 billion CFU per day of the probiotic. LGG could not be recovered from the feces of groups taking up to 150 million CFU per day. In the group taking 1.5 billion, LGG was occasionally recovered at low levels in two of the seven volunteers. In the group taking 15 billion CFU per day, all volunteers were colonized. LGG was recovered at the highest level with the highest dose—150 billion. This study showed a dose-response effect at higher dosage levels of 15 to 150 billion CFU per day required for fecal probiotic recovery.

A high-dose multistrain probiotic formula containing eight strains (three bifidobacteria, four lactobacilli and one Streptococcus) has also been shown to colonize the gut and maintain remission of ulcerative colitis (UC) in children and adults.^3-5 In children, 900 billion CFU per day of an eight-strain probiotic formula induced remission.³ In adults, 500 billion CFU per day of that same formula colonized the gut and maintained remission in UC patients.⁴ In another trial, a daily dose of 3.6 trillion CFU per day of the multistrain formula induced remission in adult patients not responding to conventional therapies.⁵

This same preparation (dosages ranging from 450 billion to 1.8 trillion CFU per day, based on weight of patient) was also found to induce and maintain remission of ulcerative colitis in children.⁶ In a randomized, double-blind, placebo-controlled trial of 29 children with UC, probiotics or placebo were added to standard treatment. In the probiotic group, 92.8 percent achieved remission compared to only 36.4 percent in the placebo group. Further, there were no biochemical or clinical adverse events related to the probiotic treatment in these children.

Two more randomized, controlled trials evaluated the effects of this probiotic preparation in twenty-five patients with diarrhea-predominant irritable bowel syndrome (IBS-D). In the first study, patients were assigned to receive either the probiotic mixture (450 billion CFU per day) or placebo for eight weeks. The multistrain probiotic relieved abdominal bloating when compared to placebo. In the second study, 48 IBS patients were randomized, double-blind, to receive either the probiotic mixture (450 billion CFU per day) or placebo for 4 or 8 weeks. The multistrain probiotic mixture reduced flatulence and slowed colonic transit without altering bowel function in patients with IBS and bloating.

In another double-blind, placebo-controlled trial, sixty patients with functional bowel disorders—non-constipation IBS, functional diarrhea and functional bloating—received a probiotic mixture of two strains, Lactobacillus acidophilus and Bifidobacterium lactis, at 200 billion CFU daily for eight weeks.⁷ Abdominal bloating improved in the probiotics group at four and eight weeks when compared to placebo. A subgroup of patients with IBS was analyzed and also found to have reduced bloating when compared to placebo.

Studies evaluating high-dose probiotics are most common for inflammatory bowel diseases, though as we see from the studies cited above, other conditions are also benefitted from a high-potency probiotic therapy. The trend toward increasing dosage of probiotics is influenced and supported by studies using doses ranging from 50 billion up to 3.6 trillion or more.

References

1. Gao XW, et al., “Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients.” Am J Gastroenterol. 2010 Jul;105(7):1636-41.
2. Saxelin M, et al., “Dose-response colonization of faeces after oral administration of Lactobacillus casei strain GG.” MicroEcol Health Dis. 1991 Jan;4:209-14.
3. Miele E, et al., “Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis.” Am J Gastroenterol. 2009 Feb;104(2):437-43.
4. Ringel Y, et al., “Probiotic bacteria Lactobacillus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders—a double-blind study.” J Clin Gastroenterol. 2011 Jul;45(6):518-25.

1. Miele E, et al., “Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis.” Am J Gastroenterol. 2009 Feb;104(2):437-43.
2. Venturi A, et al., “Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis.” Aliment Pharmacol Ther. 1999 Aug;13(8):1103-8.
3. Bibiloni R, et al., “VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis.” Am J Gastroenterol. 2005 Jul;100(7):1539-46.

1. H.J. Kim, et al., “A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating.” Neurogastroenterol Motil. 2005 Oct;17(5):687-96.
2. H.J. Kim, et al., “A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome.” Aliment Pharmacol Ther. 2003 Apr 1;17(7):895-904.

Leonard Smith, M.D.
Dr. Leonard Smith is a prominent Board-Certified, general, gastrointestinal and vascular surgeon who had a successful private practice for 25 years. In addition to his active surgery practice, he also incorporated lifestyle, diet, supplementation, exercise, detoxification, and stress management into many of the therapies he would prescribe. Many of his patients with cancer, cardiovascular disease, and other serious illnesses did so well under his treatment regimes that he began to devote most of his career to foundational health care and preventive medicine.

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Antibiotics are overused for conditions they do not treat, such as viral infections like cold or flu. Antibiotic overuse is leading to antibiotic resistance, one of the major challenges facing medicine today. But antibiotic resistance is not the only consequence of the average 10 – 20 courses of antibiotics children receive by the age of 18. An under-appreciated negative effect of too many antibiotics is the killing of beneficial bacteria, as highlighted in the recent Nature journal article, “Antibiotic Overuse: Stop the Killing of Beneficial Bacteria.”¹

From the article, written by Martin M. Blaser, head of the department of medicine at New York University’s Langone Medical Center:

“Early evidence from my lab and others hints that, sometimes, our friendly flora never fully recover [after antibiotics]. These long-term changes to the beneficial bacteria within people’s bodies may even increase our susceptibility to infections and disease. Overuse of antibiotics could be fueling the dramatic increase in conditions such as obesity, type 1 diabetes, inflammatory bowel disease, allergies and asthma, which have more than doubled in many populations.”

This gut microbiota alteration is likely a contributing factor to the increase in antibiotic resistance seen in such “superbugs” as Clostridium difficile and methicillin-resistant Staphylococcus aureus, Blaser further explained.

Studies by Les Dethlefsen, David Relman, et al, have also found permanent alterations in gut microbiota after antibiotic treatment. These researchers investigated the effects of ciprofloxacin on gut microbiota changes over a period of 8 to 10 months in two studies—one with two courses of antibiotic treatment, the other with one.^2,3 Each study involved extensive stool sample analysis by 16S pyrosequencing (one rDNA, one rRNA) in three subjects over many months.

In one study, gut composition closely resembled its pretreatment state four weeks after antibiotic treatment. However, several bacterial groups did not recover even six months later. In the second study, gut composition stabilized by the end of 10 months, but it differed from its original state. The study concluded, “Antibiotic perturbation may cause a shift to an alternative stable state, the full consequences of which remain unknown.”

Blaser recommends reducing antibiotic use during pregnancy and childhood, citing that between one-third and one-half of pregnant women receive antibiotics during pregnancy in the U.S. and developing countries. “Each generation could be beginning life with a smaller endowment of ancient microbes than the last,” he stated, “Particularly the 30 percent or so of infants born via Cesarean.”

The search for effective alternatives to traditional antibiotics is on, as researchers from all over the world are testing new possibilities in the hopes of heading off the antibiotic-resistance disaster at the pass. One recent study highlighted the use of a commensal E. coli strain which was re-engineered  by adding fragments of DNA to the bacterium that allows it to sense the presence of the pathogenic bacteria known as, Psuedomonas aerugenosa. Pseudomonas is a superbug responsible for infections in the lungs, urinary tract, blood, and on wounds and burns. Upon sensing the Pseudomonas pathogen, the E coli released a potent toxin which killed up to 90% of the pathogen.⁴ It will be exciting to see if this technology holds up in forthcoming animal and human trials.

I believe the future will likely include widespread use of large amounts of commensal bacteria, probiotic bacteria and prebiotics, as well as genetically altered bacteria, to manage bacterial infections. We may even have a whole armamentarium of slightly altered commensal/probiotic bacteria on hand for certain infections. Antibiotics are already assuming a lesser role, and the CDC has a major program to remind physicians to be more discriminating in antibiotic use.⁵ So perhaps the future of pharmaceutical antibiotics will be their judicious use, in combination with various bacterial therapies, and this will become the standard of care. It will be very interesting to watch the unfolding of all the new research.

References

1.  Blaser M, “Antibiotic overuse: Stop the killing of beneficial bacteria.” Nature. 2011 Aug 24;476(7361):393-4.
2. Dethlefsen L, et al., “The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.” PLoS Biol. 2008 Nov 18;6(11):e280.
3. Dethlefsen L and Relman DA, “Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation.” PNAS. 2011 Mar 15;108 (Suppl 1):4554-4561.
4. Saedi N, et al., “Engineering microbes to sense and eradicate Psuedomonas aeruginosa, a human pathogen.” Mol Sys Biol. 2011 Aug 16;7, no 521. Online ahead of print.
5. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6034a1.htm

Leonard Smith, M.D.
Dr. Leonard Smith is a prominent Board-Certified, general, gastrointestinal and vascular surgeon who had a successful private practice for 25 years. In addition to his active surgery practice, he also incorporated lifestyle, diet, supplementation, exercise, detoxification, and stress management into many of the therapies he would prescribe. Many of his patients with cancer, cardiovascular disease, and other serious illnesses did so well under his treatment regimes that he began to devote most of his career to foundational health care and preventive medicine.  

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allergies, antibiotic resistance, antibiotics, asthma, beneficial bacteria, childhood, Clostridium difficile, cold, flu, friendly flora, gut microbiota, inflammatory bowel disease, obesity, pregnancy, superbug, type 1 diabetes, viral infections

Over-prescription of antibiotics contributes to antibiotic resistance and affects the ability of bacteria to survive antibiotic treatment.  That’s very important because if antibiotics do not work for infections, there isn’t much else that will.  Now that’s scary!

A recent study of patients hospitalized for respiratory infections found that in those who were diagnosed with a viral infection (antibiotics will not help a viral infection) and who also had a normal chest x-ray (which detects pneumonia, which is often a bacterial infection), 63 percent were still prescribed antibiotics!  Is it perhaps just habit to prescribe them? 

Surprise, surprise:  Those patients were found to not benefit from the antibiotic treatment and, in fact, some went on to develop the antibiotic-associated Clostridium difficile infection.

This over-prescription of antibiotics is widespread, and is putting people at risk of developing dangerous infections, like C. diff, MRSA, E. coli and Klebsiella infections. In fact, two bacteria strains that carry a specific gene (NDM-1) have recently been in the news. Why?  Because bacteria that carry this gene are resistant to almost all antibiotics, including the last-resort antibiotics currently being used when the more common ones fail.

Next time your doctor wants to prescribe an antibiotic, make sure that it’s being used for a bacterial infection, and not a viral infection.

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antibiotic resistance, antibiotics, bacteria, bacterial infection, C. diff, Clostridium difficile, dangerous, E. coli, gene, infections, Klebsiella, MRSA, NDM-1, over-prescription, respiratory infection, strains, treatment

There is still a general belief with medical doctors and the public as well that Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) are mostly stress-related psychological disorders. I have personally had many patients who were reluctant to discuss their bowel problems for fear of being labeled a “psych” case. Many practitioners still aren’t aware there can be legitimate causes of disease that come from both mind and body.

With IBS and IBD, as with most discussions, there is often an element of truth on both sides or there would be no controversy. First, let’s look at the validity of the stress factors. People with genetic short serotonin transporter systems react negatively to stress-related increases in cortisol (a stress hormone) than people with normal serotonin transport systems.1 Second, ALL people react to significant stress, which can produce damage to the gut epithelial lining. However, people with a history of IBD generally show more gut lining damage than those without IBD. The damage includes: increased levels of stress hormones, activation and degranulation of mast cells, mitochondrial damage in epithelial cells, and mucosal protein oxidation which can create multiple problems with permeability (leaky gut) and immunity.2 Again, this happens to everyone under stress, but is worse with IBS and IBD because stress can trigger a relapse of either condition.

On the other hand, there are many reports that suggest anywhere from 20 to 60 percent of IBS and IBD patients have had a serious gastrointestinal infection days or weeks before they began having symptoms of chronic bloating, abdominal pain, diarrhea or constipation (or both diarrhea and constipation) that may have lasted years. A study was done on 111 patients with IBS using the lactulose breath test (measures hydrogen and methane gas produced by too many of the wrong bacteria) and 84 percent of patients were positive, which indicates small intestinal bacterial overgrowth (SIBO). Those who were treated with a non-absorbable antibiotic, Neomycin, had a statistically significant improvement both in symptoms, and normalization of the breath test.3 A more recent study4 showed that patients with IBS, but without constipation, treated with rifaximin (a broad spectrum non-absorbable antibiotic) for two weeks provided significant relief of IBS symptoms including: bloating, abdominal pain, and loose or watery stools.

Both of these studies strongly suggest that bacterial overgrowth, which creates a low-grade infection, is a major part of IBS, and can be treated with antibiotics. In addition, I think the standard of care today strongly suggests using probiotics while on antibiotics. This has been shown to lower the incidence of antibiotic associated diarrhea (AAD), and especially Clostridium difficle diarrhea, which can lead to total removal of the colon or even death.

Probiotics alone have been shown to significantly help with IBS. More specifically, probiotics enhance gut barrier function, inhibit pathogen binding and modulate gut inflammatory response. They reduce visceral hypersensitivity associated with both inflammation and psychological stress. More importantly, probiotics can alter colonic fermentation and stabilize the colonic microbiota, show that dietary exposure to pathogens maybe less likely to create another relapse of symptoms.5

Once again we can see that the use of high fiber, essential oils (omegas), probiotics and digestive enzymes (Brenda Watson’s HOPE Formula) can be beneficial in preventing or treating intestinal inflammation—be it IBS or IBD.

1. Way BM. “The Serotonin Transporter Promoter Polymorphism Is Associated with Cortisol Response to Psychosocial Stress.” Biol Psychiat. 2010 Mar 1;67(5):487-92.
2. Farhadi A, et al. “Heightened Responses to Stressors in Patients with Inflammatory Bowel Disease.” Am J Gastro. 2005;100:1796–1804.
3. Pimentel M., et al. “Normalization of Lactulose Breath Testing Correlates With Symptom Improvement in Irritable Bowel Syndrome: A Double-Blind, Randomized, Placebo-Controlled Study.” Am J Gastro. 2003;98:412-19.
4. Pimentel M., et al. “Rifaximin Therapy for Patients with Irritable Bowel Syndrome without Constipation.” N Engl J Med. 2011 Jan;364:22-32.
5. Spiller, R. “Review article: probiotics and prebiotics in irritable bowel syndrome.” Aliment Pharmacog Ther. 2008 Jun;28(4):385-96.

Leonard Smith, M.D.
Dr. Leonard Smith is a prominent Board-Certified, general, gastrointestinal and vascular surgeon who had a successful private practice for 25 years. In addition to his active surgery practice, he also incorporated lifestyle, diet, supplementation, exercise, detoxification, and stress management into many of the therapies he would prescribe. Many of his patients with cancer, cardiovascular disease, and other serious illnesses did so well under his treatment regimes that he began to devote most of his career to foundational health care and preventive medicine.

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abdominal pain, antibiotic, antibiotic associated diarrhea, bloating, body, bowel, Clostridium difficile, colon, Constipation, cortisol, Diarrhea, dietary, Digestive Enzymes, fiber, gastrointestinal, gut epithelial lining, gut lining, IBD, IBS, immunity, infection, inflammation, inflammatory bowel disease, Irritable Bowel Syndrome, lactulose breath test, microbiota, mind, Omegas, oxidation, pathogen, Probiotics, psychological, Serotonin, SIBO, small intestinal bacterial overgrowth, stress

I love it when I hear from people who have taken my advice and to learn how they have personally benefitted from it. Just look at this incredible testimonial from a woman who decided to take her health into her own hands:

“I am writing to let you know that the Ultimate Flora probiotics you recommend not only helped me recover from a debilitating disease, but made it possible for me to continue nursing my baby. In 2004, I originally came down with Clostridium difficile colitis (C. diff) and spent six months in and out of doctor’s offices and hospitals trying to get cured. Every time a course of antibiotics (first Metronidazole, then Vancocin) would stop the symptoms, they would come back as soon as I went off. It wasn’t until I did my own research and tried tapering down the antibiotics while tapering up probiotics that I got rid of the disease. But, as has been known to happen, this year (2010) it returned, after the birth of my 3rd child. After a few days of symptoms, I had a feeling what might be wrong. Sure enough, a clinical test turned up positive for C. diff. I was told that I would need to start Metronidazole right away, and that it would no longer be safe for me to nurse my baby. I told the clinician to hold off on ordering the prescription, and let me try something first. I went to my local health food store and purchased Ultimate Flora Super Critical (200 billion cultures) probiotics. After two weeks of Super Critical therapy, my symptoms were mostly gone. Two more months of daily maintenance on Critical Care (50 billion cultures), and I had no more symptoms at all. I have not relapsed in the 6 months since this happened. I am completely confident that nothing short of the Super Critical product you recommend could have cured this virulent disease. I have you to thank for my health, and that of my baby, who is still nursing at 7 months.” ~ Rachel P., Maryland

Please note C. diff is a very serious, often fatal condition and should only be treated under the care of a qualified physician. Most physicians are now treating C. diff with a combination of probiotics and antibiotics.

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Notable News

Clostridium difficile (C. diff) – More than Difficult!  Chances are you’ve probably heard of C. diff before, or at least its most common (and least pleasant) side effect – the gut-wrenching diarrhea. I know, I know, here I go talking about poop again, but this is important! C. diff infections are becoming more common every year. Studies tell us that 7,000 people are infected each day, and 300 of those die from the infection. So I say the more we know about C. diff, the better.

Okay, let’s start with the basics – just what is C. diff anyway? It’s short for Clostridium difficile, a disease-causing bacterium that most often appears after a person has taken antibiotics. This happens because the good bacteria that are normally present in the intestines (and which help keep our immunity strong) are also destroyed by antibiotics. Basically, when we take antibiotics to fight infection, they kill a lot of the good bacteria in our gut along with the bad, which disrupts our normally healthy intestinal balance. And C. diff is one of those opportunistic little buggers that will quickly take over and multiply if it has the chance, causing a potentially dangerous infection whose symptoms include severe diarrhea, abdominal cramping and nausea.

Interestingly, another culprit in the C. diff epidemic has come to light. The use of proton pump inhibitors (PPIs) has been associated with a risk for C. diff infection.  PPIs are used to treat gastroesophageal reflux disease (GERD), also known as acid reflux. These drugs suppress the secretion of acid in the stomach. 

But Wait! We Need Our Stomach Acid!  One of the functions of stomach acid is to kill bacteria that comes in with food. When there is not enough stomach acid, as occurs in people taking PPIs, harmful bacteria like C. diff can enter the intestinal tract and quickly multiply.

Can You Say Superbug? Have you heard the term Superbug?  C. diff is a Superbug. Superbugs are bacteria that become resistant to antibiotic treatment, which means that after a while, taking antibiotics won’t do anything to stop the harmful effects of the bug. Antibiotic resistance is largely the result of over-prescribing antibiotics for every little sneeze or sniffle instead of giving the body a chance to fight off the infection on its own, and it’s become a huge concern in the medical community today. I’ll talk about this more in a later post, so stay tuned!

Bottom Line? Our intestinal flora – the friendly bacteria in our intestines – play a major role in our health. One particular probiotic called Saccharomyces boulardii has been found to be especially useful for people with C. diff, particularly those that have recurrent C. diff infections. The reason is because S. boulardii is actually a yeast organism, so it’s not destroyed by antibiotics like most bacteria, which means it can keep working in the body to protect against C. diff – even if you’re taking antibiotics. The bottom line is, maintaining a good balance of beneficial microorganisms (probiotics) in the gut is a vital part of creating digestive health, which as we all know is the foundation for total-body health!

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