C.diff Archives - DSSurgery

Medication Accumulation in Gut Bacteria May Curb Drug Effectiveness, Alter Gut Microbiome

Dr. Ara Keshishian — Tue, 05 Oct 2021 22:06:00 +0000

By Marilynn Larkin September 23, 2021

NEW YORK (Reuters Health) – Many common medications such as antidepressants, diabetes and asthma drugs can accumulate in gut bacteria, altering bacterial function and potentially reducing drug effectiveness, researchers say. “It was surprising that the majority of the new interactions we saw between bacteria and drugs were the drugs accumulating in the bacteria, because up until now biotransformation (chemical modification) was thought to be the only way that bacteria affect drug availability,” Dr. Kiran Patil of the MRC Toxicology Unit, University of Cambridge, told Reuters Health by email. “We also were surprised to see the stark effect of bioaccumulation on bacterial metabolism and on community composition.” “There will likely be very strong differences between individuals, depending on the composition of their gut microbiota,” he noted. “We saw differences even between different strains of the same species of bacteria.” As reported in Nature, Dr. Patil and colleagues grew 25 common strains of gut bacteria and investigated their interactions with 15 structurally diverse oral drugs. The team identified 70 bacteria-drug interactions, 29 of which had not been previously reported. Seventeen of the newly discovered interactions could be ascribed to bioaccumulation – i.e., bacteria storing the drug intracellularly without chemically modifying it, and in most cases without bacterial growth being affected. To gain additional insight, the team investigated the molecular basis of bioaccumulation of the antidepressant duloxetine. They found that duloxetine binds to several metabolic enzymes and changes the metabolite secretion of the affected bacteria. When tested in a microbial community of drug accumulators and non-accumulators, duloxetine markedly altered the small molecules produced by the drug-accumulating bacteria, which the non-accumulators fed on; this caused an overabundance of consuming bacteria, thereby unbalancing the composition of the community. Further, the team validated their findings in C. elegans; worms grown in bacteria that accumulated duloxetine behaved differently from those grown in bacteria that did not accumulate duloxetine. Summing up, the authors state, “Together, our results show that bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, probably in an individual manner.” Dr. Patil added, “Next steps will be to take forward this basic molecular research and investigate how an individual’s gut bacteria tie in with differing individual responses to drugs such as antidepressants – differences in response, drug dose needed, and side effects like weight gain.” “If we can characterize how people respond depending on the composition of their microbiome, then drug treatments could be individualized,” he said. “The clinical relevance will hopefully be clear in the next 2-3 years.” Dr. Libusha Kelly of Albert Einstein College of Medicine in New York City commented on the study in an email to Reuters Health, “This work highlights the broad importance of microbe/drug interactions in drug bioavailability and the unrecognized potential for bioaccumulation of drugs to modify metabolite secretion in microbial communities.” “As the authors note,” she said, “this study in bacterial isolates is only the first step towards understanding how bioaccumulation might influence drug metabolism and microbial community composition in the context of the far more complicated communities of microbes in the human body.”

“There are likely additional, cryptic, ways in which bacteria alter bioavailability and drug metabolism in the human body,” she said. “Furthermore, we do not understand how microbiome/drug interactions influence drug efficacy and safety in individual patients, which limits the clinical utility of our field currently. However, the authors uncover an exciting direction for future research.” Source: https://go.nature.com/3CxioHd Nature, online September 8, 2021. Reuters Health Information © 2021

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Biofilm

Dr. Ara Keshishian — Sun, 26 Apr 2020 17:44:11 +0000

Written By: Eric Baghdasaryan, Maria Vardapetyan, Osheen Abnous

Biofilm are tiny microorganism-filled communities found throughout the human gastrointestinal tract and oral cavity. These communities adhere to both biological and non-biological surfaces within the human body. They provide their inhabitants with many competitive advantages that help these bacterial communities withstand biological, chemical, and physical stresses¹. Within these communities, microorganisms collaborate with one another to increase the likelihood of growth and multiplication despite the harsh conditions of the human gut. Not all bacteria within these biofilms are harmful, but those that are go on to cause infections and other severe health problems for the host.

Biofilm formation

Studies have shown that approximately 60-80% of bacterial infections in the human body are associated with biofilm formation. Such findings have compelled researchers to investigate the complex factors responsible for biofilm formation.

Figure 1: Biofilm adhesion, formation, and maturation. whiteley.com.au/biofilms

It was shown that bacteria anchor themselves to the mocosa surface. They collectively form a protective layer made of polysaccharides, proteins, and extracellular DNA. This forms the biofilm matrix. This biofilm matrix acts as a shield against antimicrobials, toxins, and antibodies. From here, biofilm associated bacteria go on to cause chronic infections characterized by persistent inflammation and tissue damage, initiating in the gut and adjacent regions of the gastrointestinal tract. Furthermore, some biofilm associated bacteria have shown the ability to disperse from this mature biofilm to colonize new niches, underscoring the association between local infections and systemic diseases such as atherosclerosis and rheumatoid arthritis² caused by the buildup of biofilm dispersed bacteria and subsequent inflammation in the coronary vasculature and joint capsules, respectively. In fact, BADAS syndrome (bowel associated dermatosis-arthritis syndrome) is a condition where patients present themselves with small bumps on their inner skin (mainly along the vasculature) caused by the buildup of circulating microtoxins (very small clusters of bacteria). This may lead to chronic bacteremia in the bloodstream. Also, the over circulation of host immune complexes presents many problems for the patients, such as the development of arthritis and the accompanying joint pain, caused by the build up of white blood cells in host joint capsules. Patients often link the lumps to a dermatological condition, when in reality the condition is caused by a bacterial overgrowth originating in the gut and bowel. Clinicians now believe it is very likely these bacteria are biofilm-associated and a proper early diagnosis of the biofilm origin is critical to the prevention of BADAS and similar pathologies³.

The formation of biofilms has been studied on foreign substances such as intravenous catheters, orthopedic implants, and other biomaterials that have shown device-associated infections. However, it is commonly accepted that the majority of chronic bacterial infections involve biofilm formation on natural surfaces. The pathogenic bacterial overgrowth, forming the biofilms, have been linked to major diseases of the gastrointestinal tract including Inflammatory bowel disease and colo-rectal cancer⁴.

In addition to the gastrointestinal tract, biofilms can also be formed in the oral cavity. Over 700 bacterial species reside in the oral cavity. These contribute to the outgrowth of oral biofilms (otherwise known as dental plaque, see figure 2). These oral biofilms are responsible for major oral diseases such as tooth decay, gingivitis, and periodontitis. Moreover, those with periodontal infections have significantly increased risk of cardiovascular diseases, including atherosclerosis, myocardial infarction, and stroke². The inflammation caused by oral biofilm may also be a contributing cause of conditions such as diabetes and rheumatoid arthritis¹. Therefore, the control of oral biofilm growth before the development of oral infections is critical for the prevention of these system conditions.

Figure 2: Oral Biofilm Formation.

https://phys.org/news/2018-10-scientists-infection-causing-biofilms.html

This symbiotic (mutually beneficial) relationship between gut microbiota (bacteria living in our gut) and the host begins at birth and is crucial to our overall fitness and health. However, certain external and internal factors modify the gut microbiota. This causes the formation of a pathogenic biofilm, which leads to detrimental health conditions. The same bacteria that was once helping us by maintaining a healthy gastrointestinal tract, is now triggering disease conditions⁴.

Due to bacteria’s ability to translocate, migrate, and colonize new surfaces or niches, biofilm associated infections in the gut have been linked to systemic infections in other organs, including the joints, the skin, the eyes, the vasculature, the lungs, and even the central nervous system. It is assumed that the formation of a thick mucosal biofilm might be used as a diagnostic biomarker for the onset of systemic diseases. The outgrowth of a biofilm is widely viewed as the tipping point between two alternative states: a healthy and diseased gut¹.

Figure 3. Biofilm matrix – a protective layer. Trends in Microbiology.

The biggest clinical challenge with biofilm-associated infections is their high resistance to antibiotic therapy. The effective therapeutic concentration of certain antibiotics to fight off bacteria within a biofilm (amount of the antibiotics needed in order to have positive therapeutic effects) is about 100-1000-fold higher than if the same bacteria were not associated with a biofilm². The extracellular matrix, scaffold that keeps the bacteria anchored in place, prevents the penetration of host immune cells into the biofilm, thus contributing to the increased survival of the bacterial species living within the biofilm. Bacteria living within a biofilm also undergo an increased number of mutations, leading to the generation of more antibiotic-resistant phenotypes of bacteria. Finally, studies have shown that minimal concentrations of antibiotics may actually facilitate and stimulate biofilm formation, which can be extremely problematic in clinical treatment². Therefore, to decrease the risk of biofilm induction, physicians should begin with very high doses of chemotherapeutics (antibiotics) from the very beginning of diagnosed infection. Looking ahead, there is clearly a need for novel biofilm-targeted therapies that are specifically made to prevent biofilm formation as well as eliminate the biofilm completely once it has already matured. Researchers have identified several drug candidates – DNase, lactoferrin, chlorhexidine, and taurolidine² – that they believe have the potential to effectively penetrate and destroy components of the biofilm matrix. Further research is needed to determine their efficacy.

References

Tytgat HLP, Nobrega FL, van der Oost J, de Vos WM. Bowel Biofilms: Tipping Points between a Healthy and Compromised Gut? Trends in Microbiology. January 2019;27(1): 17-25. doi:10.1016/j.tim.2018.08.009.

Marcinkiewicz J, Strus M, Pasich E. Antibiotic Resistance: a “dark side” of biofilm-associated chronic infections. Polskie Archiwum Medycyny Wewnetrznej (Polish Archive of Internal Medicine). 2013;123(6):309-312.

Dicken CH. Bowel Associated Dermatosis-Arthritis Syndrome: Bowel Bypass Syndrome Without Bowel Bypass. Mayo Clinic Proceedings. January 1984;59(1):43-46. doi:10.1016/S0025-6196(12)60341-3

Buret AG, Motta JP, Allain T, Ferraz J, Wallace JL. Pathobiont release from dysbiotic gut microbiota biofilms in intestinal inflammatory diseases: a role for iron? Journal of Biomedical Science. January 2019;26(1) doi:10.1186/s12929-018-0495-4

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Flagyl

Dr. Ara Keshishian — Wed, 25 Sep 2019 17:07:03 +0000

Flagyl is sometimes prescribed for excessive gas and diarrhea. It is an antibiotics that works well on certain bacteria that accumulates in the GI tract and contributes to the gas and the bloating.

These bad bacteria flourish when patients consume significant and excessive fiber and carbohydrates (sugars, salad, pasta etc.) The FIRST line of defense against flatulence, bloating, and diarrhea should be eleminating the culprits in the diet. This point can not be stressed enough. Adding a daily dose of yogurt may improve symptoms due to yogurts probiotic benefits. To be beneficial, Yogurt should contain live bacteria cultures, not contain artificial sweeteners or have a high sugar content.

Artificial sweetness also area source of the excessive gas and should be avoided.

The Flagyl eliminates and reduces the bad bacteria. Along with a Probiotic and healthy dietary choices Flagyl can help to significantly improved or eliminate those symptoms of gas and diarrhea.

Before Flagyl is prescribed, it is important that the diet is critically examined to make sure that the carbohydrates and the fiber as source of gas and bloating is minimized or eliminated. Excessive use of medications that may be needed for other infections should be avoided.

Chronic diarrhea should be evaluated to rule out GI infection with C. diff bacteria or other bacteria or parasite.

Additional Information on C. Diff (Clostridium Difficile) and probiotics.

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Probiotics, C. diff & Enteric Hyperoxaluria

Dr. Ara Keshishian — Sat, 26 Jul 2014 15:21:00 +0000

Probiotics have an important place in the supplement regime of a pre and post weight loss surgical (WLS) patient. It seems some DS/WLS patients may be predisposed to pathogenic bacteria overgrowth. One primary reason resulting from the alteration of the gut. Most people are dis-biotic to begin with due to western diet, etc. Weight loss surgical patients have colons which are simply far more nutrient rich than a non DS gut. The malabsorption greatly exacerbates the issue. Bacteria readily bloom under the advantageous conditions presented to them. The WLS patients’ gut is prime real estate, ripe for colonization with little or no competition from an established microbiome, pathogens can soon dominate. When we have antibiotic therapy the gut can be rapidly exposed to the very persistent C. diff spores.

There have been several questions regarding Clostridium difficult (C. Diff) and other bacterial overgrowth in the intestines. It is a gram-positive spore forming bacteria that is opportunistic. It is a small part of the normal colonic bacteria but can overgrow in people who have had antibiotic treatment. It is often spread very easily in hospitals, rehab centers or doctors’ offices. The spores live on objects for long periods of time and are not destroyed by hand sanitizers. The mode of infection is usually oral ingestion and hand washing and inflection control mechanisms can inhibit its spread. C.diff’s acid resistance nature makes it easy for the spores to travel into the intestines.

People at risk may have been on fluoroquinolones, cephalosporins, carbapenems, and clindamycin antibiotic therapy due to the destruction of the normal colonic bacterial groups. Also, daily use of medication to suppress gastric acid production is a risk factor. The low acid state does not destroy the C. diff spores.

The symptoms are flu like symptoms with moderate to severe diarrhea, abdominal pain, gas and bloating with or without fever. Complications of C. diff can lead to dehydration and colitis. Stool sampling is the usual definitive test.

Treatment for C.diff is Flaygyl, Vancomycin, or Fidaxomicin, Probiotics, hydration and possible electrolyte replacement.

Probiotics are also important in the general health of the colon. Research has shown in recent years that intestinal health can lead to improved immune function, diarrhea symptoms, improved symptoms and inflamation from Irritable Bowel Syndrome and Crohn’s Disease. Probiotic therapy is also showing great signs for treatment of H. Pylori infection, which can cause gastritis and ulceration. The Probiotic bacteria can also aid in the conversion of Vitamin K1 to Vitamin K2 although, the intestines are not the only point of Vitamin K conversion. Probiotic bacteria can improve lactose digestion in the lactose intolerant population. Probiotic use has also shown a positive effect on the weight loss, Vitamin B12 absorption and normalization of intestinal flora after RNY. Although this is not specifically DS research, we can potentially extrapolate the outcomes to DS. There is further research into Probiotic benefits in oral health, UTI and vaginal health, effect of LDL and total cholesterol absorption and bile salts hydrolase.

Calcium Oxalate Kidney Stones:

One DS specific advantage to adding a probiotic regime is the possible decrease in enteric hyperoxaluria, calcium oxalate kidney stones. Enteric hyperoxaluria is the mechanism of malabsorbed fatty acids in the colon binding with calcium thereby allowing oxalate to be absorbed into the blood stream. Also there is the theory that the unapposed bile salts may change the epithelial cells allowing oxalate absorption. “This increases the chance for oxalate kidney stone formation. Enteric hyperoxaluria is caused by jejunoileal bypass, as well as the modern bariatric procedure Roux en Y bypass. Patients with inflammatory bowel disease, pancreatic insufficiency, and intestinal resection for any reason are also at risk.” John Leske, M.D., Mayo Clinic. The fat blocking drug Zetia has also been linked to enteric hyperoxaluria. These research articles suggests that the use of Oxadrop ® probiotics, along with a low fat, low oxalate diet and increased hydration and increase calcium intake with meals, deceased the amount of oxalate absorption. Oxadrop® contains the bacteria Lactobacillus acidophilus, Lactobacillus brevis, Streptococcus thermophilus, and Bifidobacteria infantis. They suggest that the probiotic should be taken with meals and hypothesize that the probiotic bacteria possibly bind with oxalate, therefore deceasing oxalate absorption in the colon and also improve colon cells health. This is an area that needs additional study.

Another research study suggests that Oxalobacter formigenes may reduce the risk of Calcium Oxalate Kidney Stones. The study was a relatively small sample size but reports a 70% decrease in stone reoccurrence.

There are several forms of Probiotics and the following list is not meant to be inclusive. When starting a Probiotic regime there may be increased loose stool, gas and or bloating until the normal intestinal flora are re-established. In order for the beneficial flora to repopulate the intestines the pathological flora need to be eliminated. This can take time but the benefits of adding a Probiotic far outweigh the short term negative side effects. Please consult with your physician regarding any contraindications for starting probiotic therapy including allergies, medication interactions, etc.

1. Saccharomyces boulardii has demonstrated the ability to restore normal gut flora after antibiotic therapy. It is the primary constituent in Florastor and can be used at same time as antibiotic therapy. It is important to note that people with central lines, ie; PICC, central venous catheters or implantable ports should NOT take this probiotic. There have been rare cases of Fungemia reported with patients taking Saccharomyces boulardii and having central lines.

2. VSL #3 is a high-potency probiotic containing 8 diffeent strains of live lactic acid bacteria. The 8 strains are:

a. Bifidobacterium breve*

b. Bifidobacterium longum

c. Bifidobacterium infantis*

d. Lactobacillus acidophilus*

e. Lactobacillus plantarum

f. Lactobacillus paracasei

g. Lactobacillus bulgaricus

h. Streptococcus thermophile*

*Four of the strains in VSL#3 are found in the Oxadrop probiotic to possibly reduce oxalate absorption

3. Align contains Bifidobacteria infantis

In conclusion, adding probiotics to the pre and post DS supplement regime can have benefits of improved weight loss, immune function, decreasing loose stools and possibly decreasing oxalate kidney stone formation. There are many types of probiotics on the market. In the U.S., probiotics are sold as a dietary supplement and are not held to the same standard that the medication are. There is no guarantee that the types of bacteria listed on a label are effective for the condition you’re taking them for. Health benefits are strain-specific, and not all strains are necessarily useful. It is beneficial to work with your physician to decide which probiotic may be the best choice for you.

A special thank you to Dr. David Caya, D.C. for his input into this post.

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