Improvement of mental health, metabolic health, and normalization of fecal calprotectin in 4 months

Treating Clinician: Joe Mather, MD, MPH&TM

Patient Info:

• Ashley, 28 y/o, Female
• Previous Dx
  • Anxiety
  • Depression
  • Sinus Problems
  • Prediabetes – HbA1c = 6.2
  • Gastroparesis
  • Acid Reflux
• Rx
  • Lamictal
  • Spironolactone
  • Trazodone
  • Viibryd
  • Zyrtec
• Chief Complaints
  • Anxiety
  • Depression
  • Gastroparesis

Visit 1 (Day 1) – History and Exam:

Initial Impression:

• Ashley came into the office “…hoping for treatment for gastroparesis and possibly with anxiety and depression as well. GI specialist thinks gastroparesis was caused by a virus. I also got this disease right when I was dealing with a significant amount of stress.”
• ROS:
  • BM currently 1QD, soft and formed. Doesn’t float.
  • Heartburn, QD 10/10 (recently improved with Nexium) 3xQW 5
  • Bloating, QD, 8/10 (diet dependent)
  • A few episodes of mild diarrhea each week and two periods of constipation each month
  • Abd pain, 2QM, 2/10 (associated with diarrhea)
  • Constipation 2QM, 8/10
  • Bloated after eating certain foods, certain foods cause immediate diarrhea
  • Anxiety QD 5/10
  • Depression (comes and goes), 8/10
  • Skin rashes (with dairy)
  • Headaches 1QW

• Previous Testing:
  • Bravo – Stomach pH testing. Diagnosed with acid reflux
  • Colonoscopy – non-specific inflammation in the small bowel
  • Endoscopy – “small intestinal inflammation and longitudinal furrowing distal esophagus.”
  • Diagnosed with gastroparesis after a barium follow-through:
    • “Visually there is significant clearing of activity from the stomach. The est. time for clearing 50% of the activity is 115 minutes…by 180 mins, 89% of the activity has cleared. Initial normal gastric emptying time, with slight delay in emptying between hours 3 and 4”
  • Onset:
    • Childhood – Colicky baby. Had intolerance to multiple types of formula. Vomiting, reflux. “At age 9 months I went to an allergist.” Allergy testing by age 2 – sensitive to milk, corn, and eggs.
    • Constipation BM Q3-4D for most of her life.
    • March 2019 – After several breakups “I started throwing up 3-4x a week, would wake up nauseous with heartburn. Able to eat. Then usually I threw up at 8:30 am, this lasted for 6 months. Took a million TUMS and got kidney stones.” Ashley improved her diet around April and symptoms improved.
  • Prior Treatments:
    • Pantoprazole – no help
    • Zofran – “used a lot”
    • Reglan 5mg BID – fatigued and depressed
    • Erythromycin 500 TID x 2 days – “Made me worse”
    • Antibiotics – “too many to count”
  • Notes/DDX:
    • My initial impression was that chronic food sensitivities were playing a large role in her symptoms.
      • I find that if a patient reports that they were a colicky baby or with GI symptoms at a young age that they are much more likely to respond to elimination diets.
      • The finding of “longitudinal furrowing” on EGD was missed by the ordering physician. This finding is common in Eosinophilic Esophagitis – a condition.
    • High likelihood of dysbiosis, SIBO
    • As a result of poor communication with her previous physicians, Ashley was resigned to having chronic irreversible gastroparesis. This was diagnosed after a borderline study.
  • Prognosis:
    • Excellent given that she had not done basic GI work.
  • Previous Diets:
    • Dairy-free – works well

Visit 2- Testing and Initial Recommendations

Testing:

• Tests Ordered
  • GI-MAP
  • CMP, CBC w/ diff, lipid panel
  • TPO, TSH, Free T3, Free T4
  • Ferritin, iron, iron-binding capacity
  • HbA1c, Insulin
  • ANA

Recommendations:

• Diet: Paleo Diet with emphasis on eliminating dairy, wheat, sugar, and processed foods.
• GI support: Lacto-bifido blend, boulardii, soil-based probiotic, digestive enzymes, gut-healing powder
• Have the labs done, start the supplements, and told to follow up after time on diet and supplements.
• Follow up: 5 weeks

Visit 3 – Lab Interpretation

Subjective Assessment:

Lab interpretation:

• TSH 0.99 / F3 2.3 / F4 1.23 / TPO 2
• Vitamin D = 77
• Glucose 123 / HbA1c 5.3 / Insulin 34
• CBC – WBC 16.0 N 88.5%, Plt 436
• TC 218 / HDL 53 / TRI 61 / LDLc 153
• Ferritin = 40 / Iron 118 / % sat 35
• ANA – Negative
• GI Map:
  • Imbalanced flora: Streptococcus, Candida
  • Parasites, steatocrit wnl
  • Functional Markers: elastase low normal, calprotectin 2264

Diagnosis:

• Normal thyroid, Vit D, iron, ANA
• Unfortunately, Ashley had a steroid shot at urgent care 16 hours before the labs were drawn. This falsely elevated the glucose, insulin, white blood count, and neutrophils.
• In my experience, GI-MAP has poor sensitivity at detecting Candida, I generally consider any detection of Candida
• Calprotectin of 2264 is consistent with severe and advanced GI inflammation and points to the possible development of inflammatory bowel disease.

Impression:

• The shift in her HbA1c from 6.2 to 5.3 confirms that Ashley had done some dietary work prior to the labs.

Visit 4 (Email)

• Needed help with sleep

Recommendations:

• Get light exposure during the day, wear blue-blocking glasses at night
• Get 20-30 min of exercise per day (preferably outside)
• Supplements: herbal for stress hormone reduction, passionflower extract, sleep-promoting supplement

Visit 5

Subjective Assessment:

• “Supplements are helping with sleep”
• Overall, 80% better, “actually really good!”
• More energy, mentally feeling great
• Gone: constipation, heartburn, abdominal pain, bloating, diarrhea
• Still a problem: The feeling of food going up and down in the morning

Impression:

• Ashley is doing great, she is excited and much improved.

Recommendations:

• Continue diet + supplements
• Cheat meal/dessert once a week (continue to avoid dairy and wheat)
• Splenda in coffee okay
• Repeat GI-MAP in 4 weeks
• Have your other doctor shoot me an update on your chronic medications when you meet with her

Visit 6

Subjective Assessment:

• Feeling about the same since last visit, but much improved overall.
• Trailed decreasing her dose of Viibryd, felt depressed, and went back to the original dose.

Lab Interpretation:

• Repeat GI-MAP:
  • pylori +
  • Bacillus ++
  • Strep +
  • Calprotectin 464
  • Steatocrit nL
  • Elastase 381
• Despite new findings on the stool test, no need to panic. Ashley’s microbiome is stabilizing and adapting. We decided to treat with basic antimicrobials.

Recommendations:

• Start the two herbal antimicrobials
• Slowly reduce the dose of Nexium
• Consider trialing a 24h fast, or a short course of an elemental diet
• Email after 1 month to update me on your symptoms
• Retest calprotectin before the next appt

Visit 7 (Email)

Subjective Assessment:

“Just giving you my one month update. Everything has been pretty good stomach wise. We decided to not take the oil of oregano since I got really sick on it. I’ve been able to increase the other antimicrobial to 3 pills a day, instead of 4. I find that if I take two at dinner, I have diarrhea. Taking one pill of Saccharomyces boulardii and one pill of digestive enzymes. Taking two pills of each gives me diarrhea as well. No longer taking Nexium.

In our last email, you said that we would possibly add back the oregano or switch to something else.

I did not experiment with fasting. We discussed trying it if my next labs need improvement.

Also, I’m always very nauseous when I wake up. It goes away after 2-3 minutes when I sit up. This started when all my stomach issues started but it would last all morning. I’ve gotten used to it but thought you should know.”

Visit 8

Subjective Assessment:

• Couldn’t tolerate oil of oregano. Doing ok on the other antimicrobial.
  • No problem here. In some patients “less is more” with regards to antimicrobial therapy. Slow and steady nudges to the microbiome are sometimes more helpful than intense blasts, which can lead to relapses if the underlying terrain is not appropriately being helped.
• GI 100% better
• Energy levels are good
• Sleep is improving
• Anxiety + depression “really under control surprisingly, despite being trapped at home during quarantine!”
• Diet going well – no cravings. Stays away from dairy, had one cheat meal with gluten.

Lab Interpretation:

• Calprotectin – Went from over 2264 to undetectable.
  • If her calprotectin was associated with active IBD (very likely), then she has now put that IBD into remission in a matter of months.

Recommendations:

• Stop digestive enzyme, stop sleep supplement
• Finish bottle of antimicrobials
• Wait to see if symptoms creep back, and if not, discontinue gut healing powder
• Redo labs (Lipid panel, CMP, CBC w/ diff, Insulin, HbA1c)
• If all goes well, the next step in about a month is to work on reducing the probiotics and gradually on expanding the diet

Visit 9

Subjective Assessment:

• GI symptoms – gone. Occasional mild loose stools with cheat meals.
• Saw psychiatrist yesterday – Plan to decrease Lamictal. “Mentally I feel stable and good!”

Lab interpretation:

• TC 153 / HDL 41 / TRI 89 / LDL 94
• CMP, CBC – wnl
• Glucose 99 / HbA1c 5.0 / Insulin 5.2

Impression:

• Reviewed meds and supplements. Reviewed markedly improved labs.

Recommendations:

• Check-in with me in three months

Clinician’s Comments

It was fun to watch Ashley move from being resigned to living with a misdiagnosed chronic disease to thriving and improving across multiple domains.

Biochemical Markers in the Urine Associated with Gastrointestinal Mold-Overgrowth are Linked with Elevated Urinary Mycotoxins in Patients with Suspected Mold Illness

The Townsend Letter – November 2019

Study Purpose

• “It is increasingly recognized that exposure to mold and mycotoxins can lead to both acute and chronic illnesses. It is less clear at what levels these toxins are problematic. This study examined urinary mycotoxin excretion patterns in a group of patients suspected of mold-related illness compared to a group of healthy controls.”

Intervention:

• 89 healthy volunteers were compared to 103 patients suspected of mold illness
  • 7 mycotoxins were examined by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
    • “Over 400 different mold metabolites have been identified, however to date only several dozen have been shown to have significant toxic potency in humans (1)”
    • The specific mycotoxins measured were: Aflatoxin M1, Ochratoxin A, Sterigmatocystin, Zearalenone, Roridin E, Verrucarin A, Enniatin B
  • Secondarily, markers proposed to indicate colonization of the GI tract were measured

Main Results:

• The exposed patient group had more types of mycotoxins present as well as much higher levels of toxins present:
• For AFM1, the mycotoxin was detected almost four times more often in the exposed group vs the control (24.3% vs 6.1%). The mean value for the exposed group was 23 times greater (2.14 vs 0.092 ng/g creatinine) than the control group. For OTA, the exposed group had more patients with detectable OTA than the control group. The mean for OTA was 11 times higher in the exposed group vs the control (18.68 vs 1.677 ng/g creatinine). STG was positive more often in the exposed group than the control group (17.8 vs 10.9%), and the mean value was 38 times higher in the exposed group (1.75 vs 0.046 ng/g creatinine).

• Ochratoxin was found in 85% of mycotoxic patients, and in 51% of controls. The median value in the sick group was 23x high in the sick group compared to healthy controls 10.5 vs. 0.263.
  • An ochratoxin level above 10.5 gives me a high degree of confidence that a patient is mycotoxic.
• Aflatoxin was found in 24.3% of Mycotoxic patients, compared to 6.1% of controls. The mean level was 2.14 compared to 0.092 in the control group.
• Sterigmatocystin was found in 17.8% of Mycotoxic patients and in 10.9% of healthy controls. The median value in the exposed group was 1.75, compared to 0.046 in the healthy controls. This is 38 times higher.
  
• Seven proposed biomarkers for colonization were also measured and compared between the two groups. All but succinic acid had a p-value < 0.05.
• These markers are available through Great Plains’ Organic Acid Test (OAT).

• Candida is a common mold “co-infection”. It is the authors’ experience that many patients with mycotoxicity benefit from treatment with nystatin to reduce the Candidal burden.
  • Candida as well as other pathogens can infect a patient that has been exposed to mycotoxins (23).
  • To measure the amount of Candida residing in a patient, we selected citramalic as a marker, which has been shown to be produced by multiple strains of yeast (Figure 5) (26)
  • Citramalic was significantly higher in the mold-exposed group versus the control group (1.45 vs 1.02 mmol/mol of creatinine) (p-value = 0.00191).

Author Conclusion:

• “This study demonstrates that patients that are exposed to mold have elevated mycotoxins in their bodies, which can be measured by urine excretion. These mycotoxins cause multiple effects in the body. We were able to measure some of these effects through different urinary biomarkers by GC/MS.”
• “The fact that the gastrointestinal tract was colonized with mold species also indicates that patients exposed to mold that has colonized the gastrointestinal tract might continue to have severe symptoms long after moving out of a mold-contaminated environment unless treated with antifungal agents to kill gastrointestinal molds.”

Other Comments

• Hats off to GPL who took the time and effort to publish this information. For those of us working with complex chronically ill patients, it is critical that we have data like this to help guide our diagnosis and to prevent patients from being inappropriately diagnosed with mycotoxicity.
• As this study shows, Ochratoxin is by far the most commonly detected mycotoxin that we find when performing urinary testing. When using Great Plains’ testing I consider a positive test to be any Ochratoxin level above 10 as well as the detection of any of the other named mycotoxins in this study.
• While it is interesting that many of the biomarkers were higher in the exposed group compared to healthy controls, I am not yet convinced that this is evidence of colonization. Many of these metabolites can be produced by many species of organisms, and my observation is that they are sometimes elevated in a more “simple” candidal or bacterial dysbiosis. At this time, I suggest looking at these markers as additional evidence that a patient may need antifungal treatment in the gut, but not to use them as concrete proof.
• I am looking forward and hoping for additional studies to clarify if there is a single marker or two that could be followed to indicate a need for antifungal therapy.
• Citrinin and Mycophenolic Acid are also reported in GPL’s test, and these are thought to be metabolites of Ochratoxin. Occasionally you will see low levels of Ochratoxin paired with higher levels of one of these metabolites and I feel that this pattern is confirmatory of mycotoxicity.

A distinct gut microbiota composition in patients with ankylosing spondylitis is associated with increased levels of fecal calprotectin

Arthritis Res Ther . 2019 Nov 27;21(1):248. doi: 10.1186/s13075-019-2018-4.

Study Purpose

• “We aimed to define and compare the fecal microbiota composition in patients with AS, ulcerative colitis (UC), and healthy controls (HC) and to determine relationships between fecal microbiota, fecal calprotectin, and disease-related variables in AS.”

Intervention:

• Microbiota analyzed via GA-Map™, and the AS patients were assessed with questionnaires, back mobility tests, fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).
• 150 patients with AS, 18 patients with UC and 17 HC were included

Main Results

The microbiota composition in patients with AS compared with patients with UC and healthy controls

• Patients with AS, UC, and HC clustered together in distinct groups
  • “In comparison with healthy controls, the fecal microbiota in AS was characterized by a higher abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcus species, and Actinobacteria, but lower abundance of Bacteroides and Lachnospiraceae.“

Fecal microbiota composition and association to fecal calprotectin in the AS patients

• The microbiota of the AS patients with normal calprotectin was compared to patients with increased calprotectin
  • The AS patients with normal fecal calprotectin levels had higher abundance of Bacteroides, Clostridium, Prevotella, Actinomycetales, and Faecalibacterium prausnitzii, whereas patients with increased fecal calprotectin levels had a higher abundance of Bacilli class, Streptococcus genus, and Lactobacillus genus.

Dysbiosis Index score in patients with AS, patients with UC, and healthy controls

• The AS patients with the most pronounced dysbiosis, had significantly higher fecal calprotectin than the patients with DI <5.
• DI was positively correlated with fecal calprotectin (rS = 0.303; p < 0.001).

Authors Conclusion:

• Dysbiosis was found in 88% of the AS patients, and an increased dysbiosis was associated with elevation of fecal calprotectin.
  • Several of our findings indicate that there are similarities in the aberrations of the gut microbiota in IBD and AS. We found higher abundance of the phylum Proteobacteria, especially the family Enterobacteriaceae and the genus Shigella and Escherichia among the AS patients compared with healthy controls.
  • We have demonstrated a distinct fecal microbiota signature in the patients with AS, which differed from the patients with UC and healthy controls. In the AS patients, fecal microbiota signature was linked to fecal calprotectin levels, a marker of intestinal inflammation, but not to other clinical parameters. This suggests that the intestinal microbiota may be involved in an interplay with subclinical gut inflammation in AS.

Clinical Takeaways:

It is reassuring to see that the GA-Map™’s DI correlates with the clinically validated calprotectin.

Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders

Nat Commun . 2019 May 1;10(1):2012. doi: 10.1038/s41467-019-09964-7.

Note: A revisit of the study previously covered in August 2019 FFMR.

Study Purpose

• The majority of microbiome studies focus on stool, while the small intestinal microbiome remains relatively unexplored.
  • Few studies have attempted to characterize the small intestinal microbiota, primarily owing to the difficulty in accessing the small intestine and lower microbial density that makes it difficult to obtain sufficient bacterial DNA (4).
  • Recent studies comparing small bowel mucosal microbiota (obtained via either Watson capsule biopsy or enteroscopy with biopsy) in IBS patients and healthy volunteers in Sweden and in Taiwan found either no changes or IBS-associated increases in Prevotella spp., respectively (5, 6).
• “SIBO is currently defined as ≥ 10⁵ CFU/mL (colony-forming units per ml) on aspirate culture, based on the initial description in Billroth II anatomy patients with stagnant loop syndrome (15, 16, 17). “

Intervention:

• “We characterized the small intestinal microbiota of patients with GI symptoms undergoing testing for SIBO. We found significant alteration in the small intestinal microbial composition especially in a subset of symptomatic patients.”
• “In a pilot intervention study performed subsequently in healthy individuals consuming a high fiber diet, we found a short-term switch to low-fiber diet leads to change in intestinal permeability and appearance of GI symptoms associated with a change in microbial diversity.” (See Rapid-Fire research for more details on this pilot study)

Main Results:

• Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results.
• We found that small intestinal microbial composition was significantly altered in patients with GI symptoms, including significant decreases in members of genus Prevotella and enrichment of microbial ascorbate and aldarate metabolism.

Duodenal aspirate cultures do not correlate with patient symptoms

• 126 symptomatic patients were evaluated by EGD with duodenal aspirate collection; the major symptoms that led to investigation of small bowel bacterial counts included diarrhea (45%), abdominal pain (28%), and bloating (13%).
  • Of these patients, only 52% tested positive for SIBO
  • All healthy individuals tested negative for SIBO.

Duodenal aspirate microbiome is altered in symptomatic patients

• Next, the aspirate of the 126 symptomatic patients was compared with 38 healthy volunteers and the microbiome was found to be significantly different.

SIBO does not correlate with small intestinal microbial dysbiosis

• We compared the microbial composition of symptomatic patients with and without SIBO and found that SIBO does not correlate with small intestinal dysbiosis. This suggests that some symptomatic patients diagnosed with SIBO, in fact, have an overabundance of bacteria normally found in healthy microbial communities, whereas others who do not have SIBO based on quantitative assessment have dysbiosis as defined here.
  • SIBO and dysbiosis are two separate entities.

A subset of healthy individuals eating high-fiber diets have SIBO

• Healthy individuals consuming baseline high fiber diets were identified and duodenal aspirates were obtained.
  • Despite being asymptomatic, 8/16 (50%) subjects on a baseline high-fiber diet tested positive for SIBO by the standard culture criteria described above. All subjects had a microbial community composition representative of a “healthy-like” community.
    
  • This suggests that healthy individuals can have SIBO without any symptoms or alterations in microbial composition…Therefore, SIBO as currently defined may also result from dietary preferences, such as high fiber consumption, as shown here.

Authors Conclusion:

• In summary, our findings highlight the potential clinical benefit of characterizing the small intestinal microbiome. There are several mechanisms underlying the common GI symptoms such as diarrhea, bloating, and abdominal pain, and gut microbiota is likely one such factor. Small intestinal microbial compositional analysis can help identify individuals in whom the microbiome is altered and may be contributing to symptoms as well as delineate individuals with healthy small intestinal microbiome where other factors may be at play. We also provide preliminary evidence supporting the interaction of diet with small intestinal microbiota in the development of GI symptoms commonly associated with FGIDs.

Interesting Notes:

• Host factors such as advanced age, PPI, antibiotic use, and prior GI surgery explain ~ 12% of the variance in healthy and symptomatic patient microbial communities.

Clinical Takeaways:

• Symptomatic patients should be offered treatment for “non-SIBO dysbiosis” even in the advent that a SIBO breath test is negative.
• This study offers further evidence to challenge the current definition of SIBO based on duodenal aspirate.

Rapid-Fire Research: Ultra-Concise Summaries of Noteworthy Studies

Low Dose Naltrexone: Side Effects and Efficacy in Gastrointestinal Disorders

Int J Pharm Compd . Mar-Apr 2010;14(2):171-3.

• Chart review of 206 patients from GI clinic who were prescribed LDN in the setting of SIBO, chronic idiopathic constipation, or IBD. Patients with diarrhea were given 2.5 mg, constipation 2.5 BID, and IBD 4.5 mg QD.
• Side effects occurred in 61% of patients and were severe enough that one in four patients stopped (27%)
• The results in SIBO were mixed:
  • “In 85 patients with irritable bowel syndrome-small intestinal bacterial overgrowth, 15 (18%) were markedly improved, 32 (38%) were moderately worse, and 1 was markedly worse.”
• Although a smaller sample, a higher percentage benefited in CIC:
  • “In 12 patients with chronic constipation, 7 (58%) were markedly improved, 1 was moderately improved, 1 was mildly improved, and 4 (30%) were unchanged.”
• Bottom line from the study: “Low dose naltrexone frequently has side effects but in most is tolerable. It appears to be helpful for a member of patients with gastrointestinal disorders.”

Association of Healthy Lifestyle with Years Lived Without Major Chronic Diseases

JAMA Intern Med . 2020 May 1;180(5):760-768. doi: 10.1001/jamainternmed.2020.0618.

• Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best).
  • “A 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women.”
  • “Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P < .001 for dose-response). “
• Bottom line: patients who optimize their lifestyle should expect to live nearly 10 years longer without major chronic diseases.

Separating “good” from “bad” fecal dysbiosis – Evidence from two cross-sectional studies.

BMC Obes . 2018 Dec 3;5:30. doi: 10.1186/s40608-018-0207-3. eCollection 2018.

• Characterization of the microbiome using GA-Map™ in groups of subjects with morbid obesity. The researchers propose an “alternative dysbiosis index” (ADI) based on the microbiome results of obese individuals taking either metformin or artificial sweeteners.
  • Fecal dysbiosis associated with the use of metformin has been conceived as a favorable (“good”) dysbiosis and with the intake of non-nutritive sweeteners (NNS) as unfavorable (“bad”). The study aimed to construct an alternative dysbiosis index (ADI) for the separation of the dysbiosis into “good” and “bad” and to validate the ADI.
  • 76 women and 14 men aged were included. Dysbiosis was associated with the use of NNS and metformin, but not with IBS or Irritable Bowel Severity Scoring System. An ADI based on differences in 7 bacteria was positively and negatively associated with the “good” metformin dysbiosis and the “bad” NNS dysbiosis respectively.
• The researchers concluded:
  • “The new ADI, but not the DI, allowed separation of the “good” and “bad” fecal dysbiosis. Rather than merely reporting dysbiosis and degrees of dysbiosis, future diagnostic tests should distinguish between types of dysbiosis.”
• Bottom line from the study: Regardless of whether we accept the researcher’s position that shifts in the metformin are “good” and shifts from artificial sweeteners are “bad” it is likely that as profiling of the microbiome becomes more advanced we will have “subtypes” of dysbiosis that may be approached differently.

Severe intestinal dysbiosis is prevalent in primary Sjögren’s syndrome and is associated with systemic disease activity

Arthritis Res Ther . 2017 Oct 24;19(1):237. doi: 10.1186/s13075-017-1446-2.

• “Altered microbial composition of the intestine, commonly referred to as dysbiosis, has been associated with several autoimmune diseases, including primary Sjögren’s syndrome. The aims of the current study were to study the intestinal microbial balance in pSS and to identify clinical features associated with dysbiosis.”
• 42 Sjögren’s patients and 35 age-matched and sex-matched control subjects had their stool analyzed with the GA-Map™ test and evaluated with several biomarkers measuring disease activity.
  • Severe dysbiosis was more prevalent in Sjögren’s patients in comparison to controls (21% vs 3%; p = 0.018).
• Subjects with Sjögren’s and severe dysbiosis had higher disease activity as evaluated by disease severity scores, lower levels of complement, and higher levels of fecal calprotectin, compared to the other Sjögren’s patients.
• Bottom line: Severe intestinal dysbiosis is a prevalent finding in Sjögren’s Syndrome and is associated both with clinical and laboratory markers of systemic disease activity as well as gastrointestinal inflammation.

Short-term diet change alters microbial diversity and triggers GI symptoms

Nat Commun . 2019 May 1;10(1):2012. doi: 10.1038/s41467-019-09964-7.

• After the microbiome analysis provided in the study above, 16 healthy individuals consuming a high fiber diet went through a short term dietary intervention in which they were placed on a high simple sugar (low fiber) diet for 7 days. New symptoms were recorded along with new microbial mapping as well as changes in the epithelial barrier function.
  • All patients developed new symptoms, with 80% developing GI symptoms. All resolved within a week of stopping the diet.
• Both acetate and butyrate were reduced with the low fiber, high simple-sugar diet (see figure below). These microbial fermentation products are a key energy source for intestinal epithelial cells and play an important role in epithelial barrier integrity (32) and enteropathogen exclusion (33).

• Clinical bottom line: A high sugar diet negatively impacts both microbial diversity and gut barrier permeability, leading to GI symptoms.
  • “We found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability.”

Practitioner Tip

You can’t change what you don’t track.

Time management is critical for success, and an area that is frequently neglected. Consider using a device like Timular to track your time.

Tracking how you are spending your time on a day to day basis is an easy way to ensure that your work and efforts are being optimized. One option is using the Timular device. It has 8 sides which you label with various work activities (email, patient care, practice development, research…) and simply flip up when you are engaged in that activity. At the end of the week, you can look back and see how you are spending your time. This allows you to see patterns in your workday, helps you identify tasks that can be delegated to others, and helps keep you on track throughout your day. I find that simply having to be “accountable” to the device means a lot less time reading the news, and more time getting better at helping patients.