TREATMENT GUIDE FOR PHYSICIANS Metabolic Conditions · Metabolic Conditions TREATMENT GUIDE FOR...

Metabolic ConditionsTREATMENT GUIDE FOR PHYSICIANS

Obesity, type 2 diabetes, prediabetes, and non-alcoholic fatty liver disease (NAFLD) are associat-ed with many comorbidities, including stroke, liver and kidney failure, and heart disease. Current treatment for these conditions includes lifestyle interventions, dietary counseling, exercise, and pharmacologic therapies. Research suggests that an altered intestinal microbiome (dysbiosis) may also play a role in the development and progression these conditions, and as such, may present a new target area for treatment [1].

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OVERVIEW

INDICATIONS FOR SMARTGUT TESTING

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BMI >30 or BMI >25 and any comorbidities

Failure to achieve weight loss goals with diet and exercise counseling

Potential need for more invasive treatment such as medications or surgery

Abdominal obesity with waist circumference ≥102 cm (40 in) in men, or ≥88 cm (35 in) in women, PLUS any two of the following:

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• High cholesterol:

Elevated triglycerides ≥150 mg/dL or on cholesterol medication

HDL <40 mg/dL in men and <50 mg/dL in women, or on cholesterol medication

Hypertension or on antihypertensive medication

Prediabetes or diabetes

Total cholesterol ≥ 200 mg/dL

LDL ≥ 100 mg/dL

LDL ≥ 70 for people with heart disease or diabetes

SmartGut™

Metabolic Conditions PHYSICIAN’S GUIDELINES


RELEVANT SMARTGUT RESULTS

INDICATIONS FOR SMARTGUT TESTING (CONT.)

Obesity

• Low microbial diversity [2-5]

High levels of: Bacteroides [6] , Fusobacterium [2], Lactobacillus [7]

Low levels of: Akkermansia muciniphila [8,9] , Alistipes [10] , Anaerotruncus colihominis [10,11] , Barnesiella [10] , Bifidobacterium [6] , Butyrivibrio crossotus [3,4] , Butyricimonas [12] , Dialister [13] , Methanobrevibacter smithii [6,14] , Ruminococcus flavefaciens [6]

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• History of nonalcoholic fatty liver disease

Any additional metabolic-related comorbidities (e.g. polycystic ovary syndrome, sleep apnea, etc.)

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Prediabetes and Type 2 Diabetes

• In prediabetes, low microbial diversity [4]

In type 2 diabetes, high levels of: Akkermansia muciniphila [15], Barnesiella [16], Collinsella [17], Prevotella [18-20]

In type 2 diabetes, low levels of: Lactobacillus [22,23] , Roseburia [15,24]

In prediabetes, high levels of: Prevotella [18-20] , Veillonella [18]

In prediabetes, low levels of: Akkermansia muciniphila, Bifidobacterium [18], Butyricimonas [18]

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Non-Alcoholic Fatty Liver Disease (NAFLD)

• High levels of: Escherichia/Shigella, Streptococcus [25]

Low levels of: Alistipes, Flavonifractor, Odoribacter, Oscillibacter [25] •

• Suggest a Mediterranean diet: Dietary changes can change the microbiome within 24 hours of initiation. The optimal diet for patients can be variable, but in general a Mediterranean diet has been shown to improve microbiome profile [26].

Obesity, Type 2 Diabetes, and Prediabetes - Interventions to consider:

CLINICAL TREATMENT SUGGESTIONS

CLINICAL TREATMENT SUGGESTIONS (CONT.)

Obesity, Type 2 Diabetes, and Prediabetes - Interventions to consider (cont.):

• Suggest a vegetarian, vegan, or plant-based diet: If clinically appropriate, a partial or total preference for plant-based foods can significantly change gut microbiota [27]. In addition, vegetarian and vegan diets can improve insulin sensitivity, with higher effects seen 24 weeks after intervention [28].

Suggest an exercise routine: Studies show that exercise improves microbiome diversity. If patient can tolerate, recommend 30 minutes of moderate intensity 5-7 days/week [9].

Prescribe probiotics, prebiotics or synbiotics: While there have been limited clinical studies on dosing and type of probiotic for these conditions, studies have shown the following to have a beneficial effect on weight reduction and/or improved metabolic profile:

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• Recommend eliminating artificial sweeteners: Animal studies suggest that artificial sweeteners alter the gut microbiome and increase risk of obesity and metabolic disease [36].

Avoid antibiotic use when possible: This may be most important in the perinatal period and young childhood. Studies in animals suggest antibiotics during this time lead to an obese phenotype even well after antibiotics are discontinued [37,38]. An epidemiological study showed a connection between the repeated use of certain antibiotics in adults and the risk of diabetes [39].

Consider prescribing metformin for prediabetes: Animal studies have shown that metformin improves metabolic markers as well as increasing levels of Akkermansia muciniphila [40,41].

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•

Combination probiotic with Lactobacillus, Bifidobacterium, and Streptococcus thermophilus (VSL#3) [29].

The use of prebiotics and/or dietary fiber (from different plant sources) can help to restore the gut microbiome and decrease body fat [30]. The optimal dose of prebiotics is still unknown, although studies in humans suggest that the use of 10 g inulin/day or 21 g oligofructose/day may be beneficial. Sources of prebiotic fiber include soybeans, unrefined grains, bananas, tomatoes, onions, garlic, leeks, and other plant foods containing non-digestible oligosaccharides [31-34]. A multispecies synbiotic supplement (containing both prebiotics and probiotics) may help metabolic profiles in diabetic patients: L. acidophilus 2 × 109 CFU, L. casei 7 × 109 CFU, L. rhamnosus 1.5 × 109 CFU, L. bulgaricus 2 × 108 CFU, B. breve 2 × 1010 CFU, B. longum 7 × 109 CFU, S. thermophilus 1.5 × 109 CFU, and 100 mg fructo-oligosaccharide [35].




CLINICAL TREATMENT SUGGESTIONS (CONT.)

Non-Alcoholic Fatty Liver Disease - Interventions to Consider:

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Consider weight loss and regular exercise: Gradual weight loss with a low-glycemic, low-calorie diet combined with regular exercise may result in improvement in liver function tests [49].

Suggest a Mediterranean diet: Some studies suggest that a Mediterranean diet may be beneficial in improving metabolic syndrome (central obesity, elevated glucose, dyslipidemia, and hypertension), a known risk factor for NAFLD [50,51] . Additionally, a study showed that this kind of diet decreased the severity of liver disease among patients with NAFLD [52], and may improve steatosis and insulin sensitivity in individuals with NAFLD [53].

Suggest dietary modifications: Studies suggest that changes in diet may help reduce hepatic fat and inflammation:

Increase the production of short chain fatty acids by consuming fiber: Some studies have connected NAFLD-associated microbiome changes with a decrease of short chain fatty acid (SCFA) producers [64]. The production of SCFA can be enhanced by the consumption of fiber-rich foods, such as vegetables and legumes [65].

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•

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Benefits may be seen by reducing carbohydrates and saturated fat [54-57] and by increasing monounsaturated fats as well as dietary sources of omega-3 PUFAs [58-60].

Limiting consumption of all added caloric sweeteners, including high-fructose corn syrup, may also be warranted [61,62].

A study in mice showed that a low-fat diet can change fecal microbiota; in comparison with a high-fat diet, the low-fat diet also led to reversion of steatosis and a reduction in AST and ALT levels [63].

Obesity, Type 2 Diabetes, and Prediabetes - Interventions to consider (cont.):

Avoid proton pump inhibitors: Studies show these medications may alter the gut microbiome towards less healthy profiles [42,43]--for example, leading to a higher susceptibility to C. difficile-associated diarrhea [44].

Consider fecal microbiota transplant (FMT) in the future: Fecal microbiota transplant for metabolic syndrome is currently considered an investigational new drug by the FDA and requires a special permit for clinical or research use, but may become a clinical option in the future [45-47].

Consider bariatric surgery: Roux-en-Y gastric bypass (RYGB) for obesity may confer additional benefit by increasing overall gut microbial diversity [48].



POTENTIAL OUTCOMES

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• Improvement in weight, BMI, and abdominal obesity

Improvement in metabolic markers including lipid panel, blood pressure, fasting glucose

Improvement in microbiome profile towards more diversity and more beneficial microbes

Reduction in risk of diabetes, cardiovascular disease, and obesity-related comorbidities

Ability to decrease and/or avoid medication for diabetes, blood pressure, and elevated cholesterol

Improved liver function prognosis



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TREATMENT GUIDE FOR PHYSICIANS Metabolic Conditions · Metabolic Conditions TREATMENT GUIDE FOR...

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