Blood microbiota composition in Iranian pre-diabetic and type 2 diabetic patients 1

Abstract

BACKGROUND:

Type 2 diabetes as the most prevalent metabolic disorder, is one of the major causes of morbidity and mortality worldwide. Recent studies suggest that body microbiota may play a role in developing metabolic disorders including type 2 diabetes. The objective of the present study was to investigate the blood microbiota composition in Iranian pre-diabetic and type 2 diabetic patients compared to healthy individuals.

METHODS:

Blood samples were taken after 12-h fasting from 90 participants, 30 healthy individuals, 30 type 2 diabetes patients and 30 pre-diabetic participants. The buffy coat layer separated by centrifugation at 800 and DNA was extracted using a column-based method. Composition and load of blood microbiota was evaluated by real-time PCR method using genus specific 16S rRNA primers.

RESULTS:

The load of Akkermansia, and Faecalibacterium was higher in normal volunteers compared to pre-diabetic and type 2 diabetes group ( $p<$ 0.05).

The load of Bifidobacterium was higher in normal volunteers compared to type 2 diabetes patients ( $p=$ 0.02).

In contrast, the load of Lactobacillus and Escherichia coli was higher in pre-diabetics and type 2 diabetes patients compared to normal volunteers ( $p<$ 0.05).

The load of Bacteroides fragilis was not statistically different between studied groups but it was higher in males compared to female group ( $p=$ 0.04). the load of other bacteria was not significantly different between male and female participants.

CONCLUSION:

There is difference between microbiota composition in white blood cells of pre-diabetic and type 2 diabetes patients compared to healthy people. Determination of blood microbiota pattern may have a role in diagnosis and preventive of type 2 diabetes in a certain population. For more clarification about correlation between blood microbiota and type 2 diabetes, larger studies with more participants in different ethnical populations is suggested.

Keywords

Microbiota type 2 diabetes pre-diabetes

Get full access to this article

View all access options for this article.

References

Hotamisligil

G.S.

, Inflammation and metabolic disorders, Nature 444 (2006), 860–867.

Wellen

K.E.

and Hotamisligil

G.S.

, Inflammation, stress, and diabetes, J Clin Invest 115 (2005), 1111–1119.

Velmurugan

Ramprasath

Gilles

Swaminathan

and Ramasamy

, Gut microbiota, endocrine-disrupting chemicals, and the diabetes epidemic, Trends Endocrinol Metab 28 (2017), 612–625.

Pflughoeft

K.J.

and Versalovic

, Human microbiome in health and disease, Annu Rev Pathol 7 (2012), 99–122.

Shaw

J.E.

Sicree

R.A.

and Zimmet

P.Z.

, Global estimates of the prevalence of diabetes for 2010 and 2030, Diabetes Res Clin Pract 87 (2010), 4–14.

Meijnikman

A.S.

Gerdes

V.E.

Nieuwdorp

and Herrema

, Evaluating causality of gut microbiota in obesity and diabetes in humans, Endocr Rev 39 (2018), 133–153.

Stephens

R.W.

Arhire

and Covasa

, Gut microbiota: From microorganisms to metabolic organ influencing obesity, Obesity (Silver Spring) 26 (2018), 801–809.

Sircana

et al., Gut microbiota, hypertension and chronic kidney disease: Recent advances, Pharmacol Res 144 (2019), 390–408.

Olivares

et al., The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease, Gut 64 (2015), 406–417.

10.

Salonen

et al., Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men, ISME J 8 (2014), 2218–2230.

11.

Markova

N.D.

, L-form bacteria cohabitants in human blood: Significance for health and diseases, Discov Med 23 (2017), 305–313.

12.

Bhattacharyya

Ghosh

Shankar

and Tomar

, The conserved phylogeny of blood microbiome, Mol Phylogenet Evol 109 (2017), 404–408.

13.

Ghaemi

et al., Intestinal microbiota composition in iranian diabetic, pre-diabetic and healthy individuals, J Diabetes Metab Disord 19 (2020), 1199–1203.

14.

Navab-Moghadam

et al., The association of type II diabetes with gut microbiota composition, Microb Pathog 110 (2017), 630–636.

15.

Ejtahed

H.S.

et al., Main gut bacterial composition differs between patients with type 1 and type 2 diabetes and non-diabetic adults, J Diabetes Metab Disord 19 (2020), 265–271.

16.

Cani

P.D.

Osto

Geurts

and Everard

, Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity, Gut Microbes 3 (2012), 279–288.

17.

Qiu

Zhou

Jing

and Dong

, Association between blood microbiome and type 2 diabetes mellitus: A nested case-control study, J Clin Lab Anal 33 (2019), e22842.

18.

Amar

et al., Blood microbiota modification after myocardial infarction depends upon low-density lipoprotein cholesterol levels, J Am Heart Assoc 8 (2019), e011797.

19.

Munoz-Garach

Diaz-Perdigones

and Tinahones

F.J.

, Gut microbiota and type 2 diabetes mellitus, Endocrinol Nutr 63 (2016), 560–568.

20.

et al., Evaluation of QIAamp DNA Stool Mini Kit for ecological studies of gut microbiota, J Microbiol Methods 54 (2003), 13–20.

21.

D’Argenio

and Salvatore

, The role of the gut microbiome in the healthy adult status, Clin Chim Acta 451 (2015), 97–102.

22.

Karlsson

F.H.

et al., Gut metagenome in European women with normal, impaired and diabetic glucose control, Nature 498 (2013), 99–103.

23.

Qin

et al., A metagenome-wide association study of gut microbiota in type 2 diabetes, Nature 490 (2012), 55–60.

24.

K.A.

et al., Alterations in fecal Lactobacillus and Bifidobacterium species in type 2 diabetic patients in Southern China population, Front Physiol 3 (2012), 496.

25.

et al., Molecular characterisation of the faecal microbiota in patients with type II diabetes, Curr Microbiol 61 (2010), 69–78.

26.

Castillo

D.J.

Rifkin

R.F.

Cowan

D.A.

and Potgieter

, The healthy human blood microbiome: Fact or fiction? Front Cell Infect Microbiol 9 (2019), 148.

27.

Potgieter

Bester

Kell

D.B.

and Pretorius

, The dormant blood microbiome in chronic, inflammatory diseases, FEMS Microbiol Rev 39 (2015), 567–591.

28.

Traykova

Schneider

Chojkier

and Buck

, Blood microbiome quantity and the hyperdynamic circulation in decompensated cirrhotic patients, PLoS One 12 (2017), e0169310.

29.

Rajasuo

Perkki

Nyfors

Jousimies-Somer

and Meurman

J.H.

, Bacteremia following surgical dental extraction with an emphasis on anaerobic strains, J Dent Res 83 (2004), 170–174.

30.

Kowarsky

et al., Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA, Proc Natl Acad Sci USA 114 (2017), 9623–9628.

31.

Zhang

et al., Molecular investigation of bacterial communities on the inner and outer surfaces of peripheral venous catheters, Eur J Clin Microbiol Infect Dis 32 (2013), 1083–1090.

32.

Festa

et al., Chronic subclinical inflammation as part of the insulin resistance syndrome: The Insulin Resistance Atherosclerosis Study (IRAS), Circulation 102 (2000), 42–47.

33.

Mueller

et al., Differences in fecal microbiota in different European study populations in relation to age, gender, and country: A cross-sectional study, Appl Environ Microbiol 72 (2006), 1027–1033.

34.

Z.S.

and Li

, How and why men and women differ in their microbiomes: Medical ecology and network analyses of the microgenderome, Adv Sci (Weinh) 6 (2019), 1902054.

35.

Wiedermann

C.J.

et al., Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: Prospective results from the Bruneck Study, J Am Coll Cardiol 34 (1999), 1975–1981.

36.

Brown

C.T.

et al., Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes, PLoS One 6 (2011), e25792.

37.

T.K.

et al., Bifidobacterium species lower serum glucose, increase expressions of insulin signaling proteins, and improve adipokine profile in diabetic mice, Biomed Res 36 (2015), 63–70.

38.

Moya-Perez

Neef

and Sanz

, Bifidobacterium pseudocatenulatum CECT 7765 reduces obesity-associated inflammation by restoring the lymphocyte-macrophage balance and gut microbiota structure in high-fat diet-fed mice, PLoS One 10 (2015) e0126976.

39.

Kikuchi

Othman

M.B.

and Sakamoto

, Sterilized bifidobacteria suppressed fat accumulation and blood glucose level, Biochem Biophys Res Commun 501 (2018), 1041–1047.

40.

Aoki

et al., A proliferative probiotic Bifidobacterium strain in the gut ameliorates progression of metabolic disorders via microbiota modulation and acetate elevation, Sci Rep 7 (2017), 43522 .