Can We Predict Which Patients With Irritable Bowel Will Respond to Dietary Manipulation Based on Their Microbiome?

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Quote From Martin Short

In a recent post regarding Next-Generation Treatment for H pylori, the authors denigrated the term “empiric” treatment and said a more accurate term would be “hopeful” therapy. There are a lot of areas in our field in which hopeful therapy is a mainstay, especially in those with non-organic abdominal pain (eg. irritable bowel syndrome). Even with the benefit of a therapeutic ‘regression to the mean,’ treatment is often unsatisfactory.

Thus, it is a very positive sign that a recent article provides an indication of which patients are most likely to benefit from dietary manipulation:

K Vervier et al. Gut 2021;gutjnl-2021-325177. doi: 10.1136/gutjnl-2021-325177. Online ahead of print: Open Access: Two microbiota subtypes identified in irritable bowel syndrome with distinct responses to the low FODMAP diet

Methods: A prospective single centre case–control study recruited participants (n=56 pairs) from 2016 to 2019. The authors included adults (18–68 years of age) meeting the Rome IV criteria for diarrhoea-predominant or mixed type IBS (IBS-D and IBS-M, respectively) with respective household controls. 

Key findings:

  • Baseline IBS cases pre-diet identified two distinct microbiota profiles, which we refer to as IBSP (pathogenic-like) and IBSH (health-like) subtypes.
  • IBSP microbiomes were enriched in Firmicutes and genes for amino acid and carbohydrate metabolism, but depleted in Bacteroidetes species.
  • IBSH microbiomes were similar to controls.
  • On the low FODMAP diet, IBSH and control microbiota were unaffected, but the IBSP signature shifted towards a health-associated microbiome with an increase in Bacteroidetes (p=0.009), a decrease in Firmicutes species (p=0.004) and normalization of primary metabolic genes. The clinical response to the low FODMAP diet was greater in IBSP subjects compared with IBSH (p=0.02).
  • 50% of IBS cases manifested a ‘pathogenic’ gut microbial signature. This shifted towards the healthy profile on the low FODMAP diet; and IBSP cases showed an enhanced clinical responsiveness to the dietary therapy
A) Beta diversity analysis of IBS cases and healthy controls: principal coordinate analysis for the two first components identifies two distinct clusters among cases, described as cluster 1 (cl1, red) and cluster 2 (cl2, blue). Overall dispersion of household controls is represented in grey.

My take: Currently, what is a “pathogenic” microbiome is unclear at least to me. However, changes in the microbiome do occur with dietary manipulation and are likely involved in response to treatment for IBS and other disorders.

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What We Know Right Now About Omicron and About Boosters

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This article shows that the booster shot lowers the risk of death by 90% compared to those who did not receive the booster shot in those 50 years of age or older. R Arbel et al. NEJM 2021; DOI: 10.1056/NEJMoa2115624. Open Access: BNT162b2 Vaccine Booster and Mortality Due to Covid-19

Key Findings:

  • A total of 843,208 participants (50 years and older) met the eligibility criteria, of whom 758,118 (90%) received the booster during the 54-day study period. Death due to Covid-19 occurred in 65 participants in the booster group (0.16 per 100,000 persons per day) and in 137 participants in the nonbooster group (2.98 per 100,000 persons per day). The adjusted hazard ratio for death due to Covid-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% confidence interval, 0.07 to 0.14; P<0.001).

This twitter thread from Ashish Jha provides insight into the current understanding of the Omicron variant.

How To Test For Zollinger-Ellison: On or off PPI Therapy?

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S Bhattacharya et al. The American Journal of Gastroenterology: November 2021 – Volume 116 – Issue 11 – p 2216-2221doi: 10.14309/ajg.0000000000001487. Validity of Secretin Stimulation Testing on Proton Pump Inhibitor Therapy for Diagnosis of Zollinger-Ellison Syndrome

Methods: Twenty-eight patients corresponding to 29 SSTs (secretin stimulation tests) were performed on PPI, and 70 patients corresponding to 107 SSTs were performed off PPI. 

Key findings:

  • Sensitivity, specificity, and PPV of SSTs on PPI were determined to be noninferior to SSTs off PPI (P ≤ 0.05 for all).

My take: Zollinger-Ellison is a rare consideration in pediatric gastroenterology (I have only seen one case in ~ 25 years of practice). However, if testing is needed, this article indicates that stopping PPIs is probably not needed.

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

NY Times: “Who Deserves a Lifesaving Organ?”

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NY Times: “Who Deserves a Lifesaving Organ?”

Yesterday’s post discussed policy efforts to help with equitable access for transplantation. This essay explores some of the same issues.

A few excerpts:

  • What makes someone a “good” transplant candidate? Maybe it is inevitable that doctors’ biases creep in when we must make fraught decisions about a scarce resource….
  • A transplant program is also beholden to its metrics. If the one-year survival of transplant recipients is lower than expected or if transplant failure is higher than expected, a program could be put on probation or lose its certification entirely…
  • Social-support requirements vary based on the intensity of the surgery and the length of the required rehabilitation. But in general, a patient is expected to have one to three people who can commit to helping in recovery — driving to appointments, managing medications or responding to overnight emergencies…
  • So much of transplant decision-making is about narrative, which is one reason misconceptions can take hold when patients do not speak English as their primary language. Hispanic patients are about half as likely as their white peers to receive kidney donations from family or friends— a gap that Dr. Juan Carlos Caicedo, an adult and pediatric transplant surgeon who directs the Hispanic Transplant Program at Northwestern Medicine, is working to close. “People will argue that these are not good patients because they don’t follow recommendations, but they are dead wrong,” he told me. “They are great patients, as long as they understand you.”..
  • Change is happening. At my hospital, our lung transplant team is working to identify recipients from underserved communities who can become “ambassadors” to educate others and build trust…
  • Perhaps most important, transplant teams are openly discussing and challenging their assumptions about who makes a “good” transplant candidate. And in doing so, more lives may be saved.
Thanks to Jennifer for this picture

Equitable Access to Liver Transplant

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R Rosenblatt et al. Hepatology 2021; 74: 2808-2812. Open Access. Equitable Access to Liver Transplant: Bridging the Gaps in the Social Determinants of Health

The problem:

“Evaluation for organ transplantation, a life-saving procedure, involves a multistep, highly selective process. Initially, referrals to appropriate subspecialists and a transplant center are required. During evaluation, candidates undergo formal assessment of adequate social support, psychological health, health insurance, adherence, and understanding of treatments. Each step in the transplant evaluation process is an opportunity for inequity to insert itself, resulting in disparate access to listing for transplantation. This manifests through mechanisms related to poor health literacy, lack of insurance or high copay, poor social support, and geographical location. Culture incapacity by health providers and implicit bias at the provider level and health care system level can create additional barriers. Examples of health inequities include lower referral rate for LT and inferior outcomes among Black and Latinx compared to White patients,(3) while, in addition to race/ethnicity, sex and health literacy(4) also strongly correlate with the likelihood of listing. SES [socioeconomic status] affects both waitlist mortality and post-LT survival as well.”

This article proposes policy measures to counter the deleterious effects of SDOH [social determinants of health]—identify and reduce implicit bias, expand and optimize telemedicine, and improve community outreach. “Structural racism, access to affordable insurance, health literacy, and substance abuse therapy are equally important factors that contribute to health disparities and inequities and warrant further commentary and research, but are outside the focus of this policy piece.”

Related blog post: Getting a Seat at the Liver Counter

Albumin in Liver Disease -When It’s Helpful

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RK Jagdish et al. Hepatology 2021; 74: 2848-2862. Albumin in Advanced Liver Diseases: The Good and Bad of a Drug! (Review)

Useful review –

  • Explains biologic properties -typically 10-15 g of Albumin is synthesized daily (reduced in advanced liver disease). The half-life is between 12-18 days
  • Physiologic functions: oncotic effects, transports proteins/molecules/medications, antithrombotic effects, modulates inflammatory pathways
  • Main uses: beneficial in patients undergoing large-volume paracentesis or who have hepatorenal syndrome or spontaneous bacterial peritonitis.
  • Studies have shown possible modest benefit in long-term albumin administration in patients with cirrhosis, especially ANSWER study which showed a reduction in ascites recurrence, HRS, encephalopathy, infections, hospital admissions and death. Costs of long-term infusion and the lack of benefit in the ATTIRE trial indicate the need for more studies to determine the best approach in this population.
  • Main adverse effects: allergic and transfusion reactions, volume overload, antibody formation and coagulation derangements
  • Generally, albumin infusions are not recommend for correcting isolated hypoalbuminemia. The primary disorder (eg. acute stress, trauma, infection, malignancy) should be treated.

History of Medicine: Hepatitis C Discovery –“A Triumph of Curiosity and Persistence”

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MC Ghany et al. Hepatology 2021; 74: 2813-2823. Free Access: The 2020 Nobel Prize for Medicine or Physiology for the Discovery of Hepatitis C Virus: A Triumph of Curiosity and Persistence

This great little article humanizes and summarizes the discovery of Hepatitis C with first hand accounts and anecdotes.

A couple of interesting points:

  • Until you know the call is from Stockholm (and not a prank), the 4 am call informing you were awarded a Nobel prized is quite irksome
  • All of the Nobel Laureates (none are hepatologists) advocate for a vaccine but note that making it is difficult due to so many quasispecies. Only a fraction of the estimated 72 million persons with chronic HCV infection have been diagnosed and received curative therapy
  • Advice for young people: “There is no elevator to success. You have to take the stairs…It’s a step-by-step, slow process”
  • Hepatology humor:  “Is life worth living?” “It depends upon the liver.” 
Key milestones in HCV virology and therapeutics. Abbreviation: SVR, sustained virological response.

Only Tweets: PA Branding, Maternal Death Rates, Mask Mandates, Mix-Match Boosters, and Costly Way to Determine if You Have Feet

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From NPR

This article (link: PAs want to be called physician associates) notes that “Physician assistants, as they are still legally called, have been steadily granted greater autonomy over the years since 1967, when the Duke University School of Medicine graduated four former Navy medics as the nation’s first class of PAs.”

And from The Onion:

From The Onion

Quantifying the Cancer Risk (Mainly HCC) in Adults with NAFLD

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TG Simon et al. Hepatology 2021; 74: 2410-2423. Open Access. Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study

Key findings from this retrospective study with median of 14 yrs f/u (1966-2016, n=8892):

  • HCC incidence rates increased monotonically across categories of simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis (0.8 per 1,000 PYs, 1.2 per 1,000 PYs, 2.3 per 1,000 PYs, and 6.2 per 1,000 PYs, respectively; Ptrend < 0.01) and were further amplified by diabetes (1.2 per 1,000 PYs, 2.9 per 1,000 PYs, 7.2 per 1,000 PYs, and 15.7 per 1,000 PYs, respectively
  • “Compared with controls, patients with NAFLD had a17-fold higher rate of developing HCC and a 20-year absolute excess risk of 2.1%.”
  • The 20-year absolute excess risk of patients with noncirrhotic NAFLD fibrosis (4.6%) or cirrhosis (11.4%) developing HCC was comparable to that of all EHSO [extrahepatic solid organ] cancers combined (4.7% -11.4%).
  • The risk of extrahepatic solid organ cancers was increased 12% compared to general population

G Chonlakeril et al. Hepatology 2021; 74: 2336-2338 Associated Editorial. NAFLD and HCC: Time to Bridge the Gap

  • In this analysis, the authors note the annual incidence rate of HCC for cirrhosis in NAFLD was 0.62% which is below rate of 1.5% in which “HCC surveillance may be cost-effective;” however, the rate was 1.52% in those with cirrhosis and diabetes.
  • The authors note that the 9-fold higher risk for HCC in those with simple steatosis compared to matched population could be related to ascertainment bias (at least in part) as not all patients with steatosis undergo a liver biopsy; in addition, misclassification of liver biopsies is possible.

My take: Lots of increased risk with fatty liver disease, especially increased HCC/cancers and increased cardiovascular disease.

Related blog posts: