Menargetkan Mikrobiota Usus Sebagai Terapi Untuk Diabetes
Canxia He, Yujuan Shan⁎, Wei Song
School of Food Science and Engineering, Harbin Institute of Technology, Harbin 150090, China
Diabetes mellitus (DM) is becoming a common problem across the entire world. According to the latest information from the International Diabetes Federation in 2013, there are 382million
people now livingwith diabetes. And this numberwill rocket to 592 million by 2035 [1]. DM had caused 5.1 million deaths and cost 548 billion USD in healthcare expenses at the end of 2013
[1]. In 2008, a national survey in China revealed that 92.4 million adults had DM, and 148.2 million adults had pre-diabetes [2]. This high prevalence of DM in Chinamight causemore serious
diabetes-related burdens than in any other country. (See Table.) It is known that both genetic and environmental factors contribute to the pathogenesis of DM, particularly type 2 diabetes (T2D) [3–5]. Recently, studies revealed that the gut microbiota function as an important environmental factor in the development of DM [6,7]. The human gut hosts trillions of microorganisms, includingmore than 1014 bacteria belonging to 1000 species [8]. The genome size of this microbial organ, collectively termed the microbiome, exceeds the size of the human nuclear genome by 100-fold and provides humans with additional biological and metabolic functions for maintaining homeostasis in the body [9]. Numerous studies have shownthat the composition of the gut microbiota is altered in diabetic
groups. However, there are no consistent results regarding which species are altered in diabetic patients. Moreover, the detailed mechanisms linking the gut microbiota to diabetes have not been well described. Therefore, we conducted an electronic search of English articles from 2004 to 2014 in Medline to clarify the possible relationship between gut microbiota and diabetes. The MeSH search terms used were gut microbiota, diabetes, metabolic diseases, energy metabolism, immune
system, inflammation, gut permeability, and fecal transplant. In this review, we present data on the changes of the gut microbiota both in type 1 diabetes (T1D) and in T2D, and summarized the possible mechanisms through which the gut microbiota interact with diabetes. Finally, we discussed the very recent research regarding the effects of dietarymodulation and fecal transplantation of intestinal microbiota as treatment strategies for diabetes. All of these compelling lines of evidence
strongly suggest that gut microbiota might play a significant role in the development and treatment for diabetes.
Gut microorganisms and DM
The gut microbiota in our body is part of a dynamic ecosystem, and its composition is altered at the phylumand class levels by environmental and host factors which jointly influence the gut
and far removed organs. Thus, the gut microbiota is linked to several human diseases, such as obesity and diabetes [10,11]. Recently, numerous studies indicated a relationship between the gut microbiota and T2D. In 2010, Larsen et al reported that the ratios of Firmicutes to Clostridia species were attenuated in T2D patients [12]. The ratio of Bacteroidetes to Firmicutes and the ratio of the Bacteroides-Prevotella group to the C coccoides-E. rectale group were positively and significantly correlated with plasma glucose concentrations [12]. Qin et al found that Chinese T2D patients exhibited a decline in butyrate-producing bacteria (eg, Clostridiales sp. SS3/4, Eubacterium rectale, Faecalibacterium prausnitzii, etc.) and an increase in several opportunistic pathogens (eg, Bacteroides caccae, Clostridium hathewayi, C ramosum, C symbiosum and others) [13]. Moreover, the mucin-degrading species Akkermansia muciniphila and sulfate-reducing species Desulfovibrio sp. 3_1_syn3 were more abundant in T2D samples [13]. Although it is important to characterize the link between
gut microbiota and T2D, there are still some shortcomings that should be noted. For example, the entire gut bacteria population was not classified by age, gender, or drug treatment of subjects
tominimize the sources of variation. Researchwas completed in Europe that examined the composition and function of gut microbiota in a well-characterized population of 70-year-old
women [14]. In this T2Dgroup, the abundances of 4 Lactobacillus specieswere increased,whereas the abundances of 5 Clostridium species were decreased compared to individuals without
diabetes. Lactobacillus species were positively correlated with fasting glucose and glycosylated hemoglobin A1c (HbA1c). However, Clostridium species were negatively correlated to
fasting glucose, HbA1c, insulin and plasma triglycerides [14]. In an cohort of Japanese T2D patients, the numbers of Clostridium coccoides, Atopobium, and Prevotella were decreased, while the
quantities of total Lactobacillus were increased compared to those that were not diabetic [15]. This high Lactobacillus level might reflect the original numbers of bacteria in T2D patients because
no significant differences were found between the participants who consumed yogurt and those who did not. Currently, the reason for the high counts of Lactobacillus in T2D patients remains unclear. Although these independent studies revealed an association between T2D and the gutmicrobiota, some other discrepancies should not be ignored. For example, neither Akkermansia in European women nor Lactobacillus in Chinese people contribute to the compositions of gut microbiota in
T2D patients. Altered compositions of gut microbiota have also been observed in T1D patients. In a 4-matched case–control study in Finland, the gut microbiota differed between the children who
were healthy and thosewith autoimmune disorders. The striking differences included a reduced Firmicutes level and an increased
Bacteroidetes level in the children with autoimmune disorders.
Moreover, the high ratio of Firmicutes to Bacteroidetes might be an
early diagnostic marker of pending autoimmunity problems
such as T1D [16]. However, in another case–control study that
included 16 Caucasian T1D children, the numbers of Clostridium,
Bacteroides and Veillonella were all significantly increased, while
the numbers of Lactobacillus, Bifidobacterium, Blautia coccoides/
Eubacterium rectale and Prevotella were all obviously decreased
compared to normal subjects [17]. Interestingly, this study
demonstrated that the decreased number of Bifidobacterium
and Lactobacillus, aswell as thedecreased ratio of Firmicutes to
Bacteroidetes were negatively and significantly associated with
the plasma glucose level, whereas the increased numbers of
Clostridium were positively and significantly linked to a higher
level of HbA1c in the T1D group, which is completely contradictory
to the findings in T2D patients [14,17]. These results suggest that there is some degree of gut
microbial dysbiosis in diabetes, although there are differences
in the altered species. These differencesmight be attributable to
the different geographical locations, ages or gender makeup of
the populations or different food habits and analysis methods
used. Moreover, there are still some questions that remain
unresolved regarding the association between gut microbiota
and diabetes. For example, whether the alterations in the
gut microbiota in diabetes are the causes or the consequences
of the diabetic pathology. Hence, the interactions between
diabetes and gut microbiota are more intricate than what we
previously believed. Further studies are required to investigate
the roles of gut microbiota in diabetes.
School of Food Science and Engineering, Harbin Institute of Technology, Harbin 150090, China
Diabetes mellitus (DM) is becoming a common problem across the entire world. According to the latest information from the International Diabetes Federation in 2013, there are 382million
people now livingwith diabetes. And this numberwill rocket to 592 million by 2035 [1]. DM had caused 5.1 million deaths and cost 548 billion USD in healthcare expenses at the end of 2013
[1]. In 2008, a national survey in China revealed that 92.4 million adults had DM, and 148.2 million adults had pre-diabetes [2]. This high prevalence of DM in Chinamight causemore serious
diabetes-related burdens than in any other country. (See Table.) It is known that both genetic and environmental factors contribute to the pathogenesis of DM, particularly type 2 diabetes (T2D) [3–5]. Recently, studies revealed that the gut microbiota function as an important environmental factor in the development of DM [6,7]. The human gut hosts trillions of microorganisms, includingmore than 1014 bacteria belonging to 1000 species [8]. The genome size of this microbial organ, collectively termed the microbiome, exceeds the size of the human nuclear genome by 100-fold and provides humans with additional biological and metabolic functions for maintaining homeostasis in the body [9]. Numerous studies have shownthat the composition of the gut microbiota is altered in diabetic
groups. However, there are no consistent results regarding which species are altered in diabetic patients. Moreover, the detailed mechanisms linking the gut microbiota to diabetes have not been well described. Therefore, we conducted an electronic search of English articles from 2004 to 2014 in Medline to clarify the possible relationship between gut microbiota and diabetes. The MeSH search terms used were gut microbiota, diabetes, metabolic diseases, energy metabolism, immune
system, inflammation, gut permeability, and fecal transplant. In this review, we present data on the changes of the gut microbiota both in type 1 diabetes (T1D) and in T2D, and summarized the possible mechanisms through which the gut microbiota interact with diabetes. Finally, we discussed the very recent research regarding the effects of dietarymodulation and fecal transplantation of intestinal microbiota as treatment strategies for diabetes. All of these compelling lines of evidence
strongly suggest that gut microbiota might play a significant role in the development and treatment for diabetes.
Gut microorganisms and DM
The gut microbiota in our body is part of a dynamic ecosystem, and its composition is altered at the phylumand class levels by environmental and host factors which jointly influence the gut
and far removed organs. Thus, the gut microbiota is linked to several human diseases, such as obesity and diabetes [10,11]. Recently, numerous studies indicated a relationship between the gut microbiota and T2D. In 2010, Larsen et al reported that the ratios of Firmicutes to Clostridia species were attenuated in T2D patients [12]. The ratio of Bacteroidetes to Firmicutes and the ratio of the Bacteroides-Prevotella group to the C coccoides-E. rectale group were positively and significantly correlated with plasma glucose concentrations [12]. Qin et al found that Chinese T2D patients exhibited a decline in butyrate-producing bacteria (eg, Clostridiales sp. SS3/4, Eubacterium rectale, Faecalibacterium prausnitzii, etc.) and an increase in several opportunistic pathogens (eg, Bacteroides caccae, Clostridium hathewayi, C ramosum, C symbiosum and others) [13]. Moreover, the mucin-degrading species Akkermansia muciniphila and sulfate-reducing species Desulfovibrio sp. 3_1_syn3 were more abundant in T2D samples [13]. Although it is important to characterize the link between
gut microbiota and T2D, there are still some shortcomings that should be noted. For example, the entire gut bacteria population was not classified by age, gender, or drug treatment of subjects
tominimize the sources of variation. Researchwas completed in Europe that examined the composition and function of gut microbiota in a well-characterized population of 70-year-old
women [14]. In this T2Dgroup, the abundances of 4 Lactobacillus specieswere increased,whereas the abundances of 5 Clostridium species were decreased compared to individuals without
diabetes. Lactobacillus species were positively correlated with fasting glucose and glycosylated hemoglobin A1c (HbA1c). However, Clostridium species were negatively correlated to
fasting glucose, HbA1c, insulin and plasma triglycerides [14]. In an cohort of Japanese T2D patients, the numbers of Clostridium coccoides, Atopobium, and Prevotella were decreased, while the
quantities of total Lactobacillus were increased compared to those that were not diabetic [15]. This high Lactobacillus level might reflect the original numbers of bacteria in T2D patients because
no significant differences were found between the participants who consumed yogurt and those who did not. Currently, the reason for the high counts of Lactobacillus in T2D patients remains unclear. Although these independent studies revealed an association between T2D and the gutmicrobiota, some other discrepancies should not be ignored. For example, neither Akkermansia in European women nor Lactobacillus in Chinese people contribute to the compositions of gut microbiota in
T2D patients. Altered compositions of gut microbiota have also been observed in T1D patients. In a 4-matched case–control study in Finland, the gut microbiota differed between the children who
were healthy and thosewith autoimmune disorders. The striking differences included a reduced Firmicutes level and an increased
Bacteroidetes level in the children with autoimmune disorders.
Moreover, the high ratio of Firmicutes to Bacteroidetes might be an
early diagnostic marker of pending autoimmunity problems
such as T1D [16]. However, in another case–control study that
included 16 Caucasian T1D children, the numbers of Clostridium,
Bacteroides and Veillonella were all significantly increased, while
the numbers of Lactobacillus, Bifidobacterium, Blautia coccoides/
Eubacterium rectale and Prevotella were all obviously decreased
compared to normal subjects [17]. Interestingly, this study
demonstrated that the decreased number of Bifidobacterium
and Lactobacillus, aswell as thedecreased ratio of Firmicutes to
Bacteroidetes were negatively and significantly associated with
the plasma glucose level, whereas the increased numbers of
Clostridium were positively and significantly linked to a higher
level of HbA1c in the T1D group, which is completely contradictory
to the findings in T2D patients [14,17]. These results suggest that there is some degree of gut
microbial dysbiosis in diabetes, although there are differences
in the altered species. These differencesmight be attributable to
the different geographical locations, ages or gender makeup of
the populations or different food habits and analysis methods
used. Moreover, there are still some questions that remain
unresolved regarding the association between gut microbiota
and diabetes. For example, whether the alterations in the
gut microbiota in diabetes are the causes or the consequences
of the diabetic pathology. Hence, the interactions between
diabetes and gut microbiota are more intricate than what we
previously believed. Further studies are required to investigate
the roles of gut microbiota in diabetes.
Komentar
Posting Komentar