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Importance of Microbial Diversity

Importance of Microbial Diversity

The gut microbiome—the microbial community in the intestinal tract—is an influencer of metabolism and immunity and a mediator of resistance to some pathogenic infections.1

Essential gut microbiome
Bacteria_new

A distinct and essential organ within the human body, the gut microbiome contains an estimated 500-1000 species and 100 trillion organisms, encoding 100-fold more unique genes than our own genome.1-4

In its balanced state, there is a symbiotic relationship between luminal bacteria and our human cells.5

These cells communicate and form long-lasting, interactive associations that play a vital role in conservation of mucosal immune function, epithelial barrier integrity, motility, and nutrient absorption.5-7

Dysbiosis is the disruption of the composition and/or diversity of the gut microbiome. The causes can be attributed to stress, diet, hygiene, and use of antibiotics. Dysbiosis has been associated with a range of different gastrointestinal (GI) and non-GI diseases including neurologic, metabolic, liver, inflammatory, and infectious diseases. Restoration of the gut microbiome homeostasis is essential to rectifying dysbiosis.5,8,9 While this often occurs as a natural process, therapeutic intervention may also be required.

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Dysbiosis and C. Diff Infection

The gut microbiota generally play a role in colonization resistance by which the native organisms prevent pathogenic microbes from flourishing. Disruption of the gut microbiome leads to an environment suited for the proliferation of Clostridioides difficile (C. diff).5,10

Healthy gut flora and Gut flora in a dysbiosis state

When the relationship between the gut and its healthy flora becomes imbalanced, dysbiosis results…

…leading to an intestinal microenvironment susceptible to pathogenic insult from opportunistic bacteria, such as C. diff—capable of causing a wide spectrum of symptoms ranging from mild diarrhea to sepsis.5

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C. Diff Infection: An Urgent Public Health Threat

A major and urgent threat, according to the US Centers for Disease Control and Prevention (CDC), C. diff infection is one of the most common health care-associated infections in US hospitals, affecting approximately half a million people annually.11,12

Significant comorbidities exist with C. diff infection:

Infection in the blood stream

Sepsis

27%13

A heart beating

Heart Failure

43%14

Portion of the intestines being removed

Bowel Surgery

7%13

Removing sections from the colon

Colectomy

6%13

Arrows around a patient symbolizing recurrence

Re-recurrence

50%15

Mortality associated with C. diff infection:

30-day mortality rate of C. diff infection ranges from 5% to 14% after initial episode12.16

A study of Medicare patients with community-acquired C. diff infection documented a 9% mortality rate during inpatient stay.17

The relationship between patients with C diff infection and COVID-19 virus

In a recent CDC research letter, patients (N=9) with severe acute respiratory syndrome coronavirus 2 (COVID-19) and C. diff infection had a 44% mortality rate.18

Unfortunately, C. diff infection may be the beginning of a vicious cycle of recurrence.

Recurrent C. Diff Infection Affects Patient Quality of Life, Hospital Quality Metrics, and Reimbursement

C. diff infection recurs in up to 35% of cases within 8 weeks after initial C. diff infection diagnosis.12

Recurrent C. diff infection significantly affects hospital quality metrics and reimbursement. 37% of patients suffering with recurrence are hospitalized at least 3 separate times. Hospitalizations average 18 days. The total, all-cause, and direct medical costs during 12-month period after initial C. diff infection can range from $131K to $207K.14,19,20

recurrent-c-diff-infection-burden-chart
recurrent-c-diff-infection-burden-chart

Total, all-cause, direct medical costs during 12-month period after initial C. diff infection.20

Recurrence accounts for some 75,000 to
175,000
additional cases of C. diff infections
per year in the United States.21,22 Furthermore,
patients who have had a recurrence are at a
higher risk of further C. diff infections.23

RECURRENCE ACCOUNTS FOR SOME
75,000 TO 175,000
ADDITIONAL CASES OF C. DIFF
INFECTIONS PER YEAR IN
THE UNITED STATES.21,22

After the first recurrence, it has been estimated that up to 60% of patients may develop a subsequent recurrence.14,24

In fact, one observational analysis found that 84% of patients with recurrent C. diff infection will have a C. diff infection-related readmission within 12 months.25

A systematic literature review found that patients with 3 or more recurrences had a mean of 5.8 inpatient visits and 4.6 emergency department visits per patient in a 12-month follow-up period.20

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Antibiotics: The Standard of Care for C. Diff Infection Is Also a Predominant Risk Factor for Recurrence

Up To 35%

While antibiotics are the standard of care for the treatment of C. diff, their use is also a predominant risk factor for recurrence. Up to 35% of patients will experience recurrence within 8 weeks after initial C. diff infection diagnosis.12

Antibiotic use has been shown to disrupt the ecology of the human microbiome and is associated with increased risk of deadly infections such as recurrent C. diff.26

Disruption of microbiota increases the risk of C. diff infection by providing a niche for the bacteria to flourish.
Should the intestinal microbiota be disrupted by antibiotics, the effects may be long-lasting and the risk of C. diff infection may increase during continued therapy. Longer exposure to multiple antibiotics and treatment with multiple antibiotics may increase the risk.27

Thus starts a cycle of C. diff infection and reinfection— impeding microbiome recovery, exacerbating morbidity, and creating a substantial economic burden.28

Restoring a healthy gut microbiome is increasingly accepted as a promising treatment option for recurrent C. diff infection.29

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Current Therapeutic Options for Gut Microbiome Restoration Are Limited

The aim of microbiome restoration is to repopulate a diverse gut microbiota to treat disease. For recurrent C. diff infection, one historic approach has been fecal microbiota transplant (FMT).29

Most studies assessing the benefits of FMT are retrospective case series or systematic reviews of contrasting sources of microbiota and limited safety data.30-32

The lack of product standardization and administration methods has created a situation where a regulated, safe, and effective product is critically needed.33 In fact, as recently as March 2020, the FDA issued a warning of the potential risk of serious or life-threatening infections following investigational use of an FMT product supplied by a US stool bank company.34

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Further research is essential to ensure availability of a safe, effective, and standardized microbiota-based therapeutic that can help—along with antibiotic treatment—restore the microbiome and break the viscous cycle of recurrent C. diff infection.

RESTORE THE GUT MICROBIOME

RESTORE HOPE IN PATIENTS WITH RECURRENT C. DIFF INFECTION

Resources

Gain a greater understanding of the role of the gut microbiome and the burden of C. diff infection with these downloadable resources and links.

Infographic: The Threat and Burden of C. Diff Infection

Resources Image

View Mechanism of CDI Video
Take a closer look at C. difficile infection and the role of the gut microbiome.

Explore the MOD of C. difficile and its role in disease

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References

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