Condition-Specific Effects of Synbiotics

Synbiotics are combinations of pre, post, and probiotics. They offer benefits to a range of health conditions.

Key points

  • Synbiotic supplements could help to modulate intestinal permeability
  • Reviews of the evidence show benefits from synbiotic supplementation on a range of health conditions, including cancer and cardiometabolic, neurological, and gastrointestinal conditions

Synbiotic supplementation is a relatively new concept (when compared to supplementing with pre- and probiotics) that has a large body of emerging research on its potential uses for health.

[See the previous article on the overall health effects of Synbiotics]

Synbiotics and ‘leaky gut’

Synbiotics might play a role in modulating inappropriate gut permeability (commonly called ‘leaky gut’). The gut wall is permeable by nature to allow for greater or lesser ingress of nutrients into the system. The amount of permeability shifts constantly and is influenced by many factors. Increased intestinal permeability which may be inappropriate for optimal immune, allergy, and inflammatory modulation is influenced by diet and lifestyle factors, especially the gliadin protein (a component of gluten) and by small intestinal bacterial overgrowth and dysbiosis.1 Therefore, our diet and lifestyle, including factors like a typical Western-style diet high in gluten-containing ultra-refined foods, sugar, and other factors like stress and lack of movement (which affect gut motility) are likely to play a role in ‘leaky gut’ and resultant immunological and inflammatory challenges.  A primary modulator of intestinal permeability is the protein zonulin. Synbiotic supplementation reduces zonulin levels,2 and so, might play a role in reducing excessive intestinal permeability and might even help to reduce muscle wasting by reducing intestinal permeability. A 2021 review by Krimpen and colleagues found that Lactobacillus and Bifidobacterium reduce muscle wasting in mice and that there is an association between gut permeability and muscle mass. Thus, they proposed that some interaction of lactate, butyrate, and reduced inflammation from probiotic or synbiotic supplementation might help to prevent muscle wasting.3

Synbiotics in critical illness and surgery

Synbiotics and probiotics increase levels of the beneficial short-chain fatty acids acetic acid, butyric acid, and propionic acid, and reduce c-reactive protein and interleukin-6. They have been shown to reduce surgery-related complications including abdominal distention, diarrhoea, pneumonia, sepsis, surgery site and urinary tract infection, and reduce the duration of antibiotic therapy, postoperative pyrexia, time of fluid introduction, time-to-solid diet, and duration of hospital stay.4-11 It has been concluded that perioperative synbiotics “clearly reduce infection after liver surgery”.12

A 2016 review that compared the effects of synbiotics and probiotics found that there was a greater improvement in infection rates in studies of probiotics compared to those conducted on synbiotics, however, the authors noted there was limited clinical data available at the time for synbtioics.13

Metabolic disorders

Prediabetes & non-alcoholic fatty liver disease

Reviews of randomised controlled trials have shown that synbiotic supplementation can improve body mass, blood glucose, insulin, LDL and total cholesterol, triglycerides, inflammatory markers c-reactive protein and tumour necrosis factor-alpha (TNF-α), and liver enzymes alanine transaminase and aspartate transaminase14 and GGT15  levels among patients with non-alcoholic fatty liver disease (NAFLD). 14, 16, 17

Diabetes

Synbiotics supplementation significantly improves fasting blood glucose, insulin, HOMA-IR, insulin sensitivity (QUICKI) and triglycerides, V-LDL, LDL, HDL and total cholesterol.18-20 Synbiotic supplementation also reduces the inflammatory markers TNF-α, malondialdehyde, and c-reactive protein in people with diabetes21, 22 while also increasing total antioxidant capacity and glutathione.22

Obesity

Synbiotic supplementation is known to reduce fasting insulin and triglyceride levels, an effect also observed in people with obesity.23A meta-analysis of 23 randomized trials indicated that supplementation with synbiotic can decrease body weight and waist circumference.24 A 2019 review also found that while overall no significant effects from probiotic or synbiotic supplementation were observed for metabolic and anthropometric markers in children and teens, sub-group analysis revealed a significant reduction in body mass index (BMI) z-score in the synbiotic supplemented groups.25 Similarly, another review and meta-analysis from the same year found no difference in body weight or BMI but a significant reduction in waist circumference (of less than 1 cm).26 The most recent review in this area included here (from 2020) found significant reductions in BMI, total body fat, waist circumference, and waist height ratio27 (an important indicator of metabolic health and disease risk).

Blood pressure

Synbiotics have been shown to reduce systolic blood pressure by around 3 mmHg and blood pressure reducing effects were greater with longer-term supplementation (i.e., > 12 weeks) and in younger people.28

Respiratory infections

Overall, synbiotic interventions reduce the incidence rate of respiratory infections by ~16%. Subgroup analysis also suggested more prominent effects of synbiotics among adults than infants and children.29

Asthma

In a review of 11 randomised trials including over 1600 children, while no association was found between probiotic use and asthma risk, a significant reduction in asthma risk was observed in those taking pre- or synbiotics.30

Pneumonia

Network meta-analysis has shown that synbiotics, especially Bifidobacterium longum + Lactobacillus bulgaricus + Streptococcus thermophiles, B. longum + L. bulgaricus + S. thermophiles and Lactobacillus rhamnosus were superior to placebo in preventing ventilator-assisted pneumonia. Analysis was performed to rank the treatments, finding that the most efficacious treatment for preventing pneumonia of this type was B. longum + L. bulgaricus + S. thermophiles.31

Pancreatitis

Patients treated with pro-, pre-, or synbiotics had significantly shorter hospital stays and a lower risk of organ failure compared to control.32

Cancer

Both probiotics and synbiotics might help prevent colorectal cancer, likely through mechanisms including modulating the intestinal microbiota, reducing inflammation, inducing apoptosis and inhibiting cancer cell growth, modulation of immune responses and cell proliferation, enhanced intestinal barrier function, modulation of oxidative stress, and production of anti-carcinogenic compounds in the gut.33 Synbiotics also have a positive effect on diarrhoea, symptomatic intestinal obstructions, surgical infections and pneumonia in cancer patients undergoing colorectal resection.34

Pregnancy

Synbiotic supplementation might reduce anxiety in perinatal women.35 Synbiotic supplementation also reduces insulin and improves insulin homeostasis in pregnant women,36 and in those with gestational diabetes reduces inflammation, improves antioxidant capacity, and reduces insulin and very-low-density lipoprotein. Supplementation during pregnancy was also associated with reduced risk of hyperbilirubinemia in the newborn and improved birth weight.37

Mental health

Synbiotics may modulate depression and anxiety but at this time, the research is inconclusive and pro- and synbiotics might affect mental health conditions in a strain-specific manner.38

Irritable bowel syndrome

Synbiotics significantly improve global IBS scores compared to placebo.39

Chronic kidney disease

Synbiotic supplementation significantly reduces inflammatory markers CRP and MDA11, 40 while increasing the antioxidant glutathione in chronic kidney disease patients, as compared to placebo. Subgroup analyses showed that other key factors, such as the duration of intervention, participants’ baseline body mass index (BMI), type of intervention, and age, had an effect of microbial therapies on outcomes.40 Synbiotics might also reduce total cholesterol, fasting blood glucose, and improve insulin sensitivity.11

Pancreatitis

Use of pre-, pro-, and synbiotics shorten the length of hospital stay in severe acute pancreatitis.41

Autism spectrum disorder

A 2021 review by Tan and colleagues concluded that at this time results from the extant research do not support that probiotics are beneficial for ASD but that synbiotics appear to be effective in reducing some behavioural symptoms of ASD.42

Autoimmune conditions

Overall, pro- and synbiotic therapies have been shown to reduce inflammatory markers (CRP, IL-6, TNF-a, MDA) and improve insulin homeostasis in people with autoimmune conditions.43

Inflammatory bowel diseases

Pro-, pre-, and synbiotics increase Bifidobacteria and can improve remission rates and reduce disease activity in ulcerative colitis. Synbiotics appear to be more effective than either pre- or probiotics.44 Synbiotics also significantly improve endoscopic and histological scores, clinical disease activity, c-reactive protein, intestinal microbiota, bowel habits and levels of mRNA, TNF-a, interleukin1a, interleukin-10 and modulates pro- and anti-inflammatory colonic cytokines.45

Polycystic ovary syndrome

Pro-, and synbiotic supplementation reduce insulin and triglycerides,46  free androgens and the inflammatory marker MDA, and increases sex hormone-binding globulin and nitric oxide in women with PCOS.47 Effects on fasting blood glucose, HOMA-IR, c-reactive protein, and total testosterone were previously thought to be equivocal,46, 48 but meta-analysis published in 2020 and 2021 suggest improvement in insulin and insulin homeostasis.49, 50 In a 2018 review it was noted that although significant, the reduction in triglycerides was negligible.46 However, this amounted to a reduction of ~0.2 mmol/L, which is clinically meaningful. Subgroup analysis has also suggested that probiotics are associated with greater reductions in testosterone and post-prandial glucose while synbiotics resulted in a more pronounced reduction in fasting blood insulin.49

Diarrhoea

Treatment with pro- or synbiotics significantly reduces the duration of diarrhoea,51, 52 hospitalisations,51 and hospital stay-length52 in severe cases of diarrhoea in children.

Stomach ulcers

Helicobacter pylori overgrowth is commonly implicated as either causal or comorbid with gastric ulcers. Synbiotics might help to reduce complications of stomach ulcers by improving H. pylori eradication rates and reducing adverse events of antibiotic therapy.53

Cognition

Early studies in elderly people with cognitive decline suggest that pro- and synbiotics might improve cognition.54

Eczema

A meta-analysis of 6 randomised controlled trials  found significant reductions in the clinical severity of atopic eczema in children when mixed bacteria were used and by children over 1 year of age.55

Summary

Synbiotics offer the potential to improve a host of health conditions. They have been demonstrated to positively influence the gut microbiota and have demonstrated functional benefits for a range of health conditions. Their effects are likely to be due to gut-modulated and associated improvements in immunological and inflammatory modulation.


Check out Part 1. The Health Benefits of Synbiotics


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References

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