Application of Fuxia dothidei YG0564 in preparation of composition for promoting height development of juveniles

Abstract

The invention relates to the field of microorganisms, in particular to application of Fuxia dolferi YG0564 in preparation of a composition for promoting height development of juvenile subjects and the composition for promoting height development of the juvenile subjects. According to the invention, it is found for the first time that the Fuxia dolferi YG0564 can promote the height development of juvenile subjects, and especially in a malnutrition diet mode, the effect of promoting the height development of the juvenile subjects is more remarkable. In addition, the composition provided by the invention contains two active ingredients, namely, the Fuxia dolferi YG0564 and the HMO, and the two active ingredients have a remarkable synergistic effect in the aspect of promoting height development of juvenile subjects. Therefore, the problem that the height development of the children in the malnutrition mode lacks an effective probiotic solution is effectively solved, and powerful support is provided for improving the height development condition of the children in the special diet mode.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of microorganisms, in particular to the application of Phocaeicola dorei YG0564 in the preparation of a composition for promoting the height development of minors and a composition comprising the same. BACKGROUND

[0002] In recent years, the research on probiotics in the field of children's height development has gradually become a hot topic, but the research scope is mostly limited to traditional strains such as lactobacillus and bifidobacterium. Existing research shows that although these traditional strains show certain growth-promoting potential in some experiments, their growth-promoting effect has significant limitations, and the mechanism of action of the strain function is not clear. For example, the lactobacillus casei LC89 and bifidobacterium longum infantis BI03 of Weikang probiotics, although these two strains can promote bone growth and increase body weight in mouse experiments, their growth-promoting effect has not been fully verified under the simulated malnutrition diet mode, and it is difficult to meet the actual needs of children's height development under different nutritional conditions.

[0003] As a core active ingredient of breast milk, HMO (human milk oligosaccharide) has been widely researched and applied in infant formula milk powder field. Existing research and application mainly focus on its positive role in enhancing immunity and maintaining intestinal barrier integrity. However, relevant research has found that the use of HMO alone has a weak promoting effect on children's height development, and can only slightly increase the level of growth hormone (GH) and blood phosphorus, which cannot effectively meet the urgent needs of children's height growth during the growth and development process, and it is urgent to explore new application methods or combination schemes to improve its promoting effect on children's height development. SUMMARY

[0004] Invention objectives

[0005] The purpose of the present application is to provide the use of Phocaeicola dorei YG0564 in the preparation of a composition for promoting the height development of minors, which is preserved in the China General Microbiological Culture Collection Center, and its classification name is Phocaeicola dorei, the preservation date is June 7, 2023, and the preservation number is CGMCC No. 27578.

[0006] In addition, the present application also provides a composition for promoting the height development of minors, which comprises the above-mentioned Phocaeicola dorei YG0564 and human milk oligosaccharide; the Phocaeicola dorei YG0564 and human milk oligosaccharide show obvious synergistic effect in promoting the height development of minors.

[0007] Solution

[0008] To achieve the object of the present application, the present application adopts the following technical solutions.

[0009] In a first aspect, the present application provides the use of Phocaeicola dorei YG0564 in the preparation of a composition for promoting the height development of a minor subject, wherein the Phocaeicola dorei YG0564 is deposited with the China General Microbiological Culture Collection Center, and the classification name is Phocaeicola dorei, the deposit date is June 7, 2023, and the deposit number is CGMCC No. 27578.

[0010] In a feasible implementation, the minor subject is a malnourished minor subject.

[0011] In a feasible implementation, in the composition, the Phocaeicola dorei YG0564 is used as the only effective component or as one of the effective components.

[0012] Preferably, the effective component of the composition further comprises a breast milk oligosaccharide.

[0013] Further preferably, the breast milk oligosaccharide is selected from 2'-fucosyllactose, lacto-N-neotetraose, 3'-sialyllactose, lacto-N-tetraose and 6'-sialyllactose, further preferably 2'-fucosyllactose and / or lacto-N-neotetraose, and most preferably 2'-fucosyllactose.

[0014] Further preferably, the ratio of the Phocaeicola dorei YG0564 and the breast milk oligosaccharide is (10 8 -10 10 ) CFU: (20-500) mg, further preferably (5 x 10 8 -5 x 10 9 ) CFU: (50-200) mg, and most preferably 10 9 CFU: 100 mg.

[0015] In a feasible implementation, the promotion of the height development comprises:

[0016] (1) improving malnutrition-related growth retardation;

[0017] (2) promoting height growth; and / or,

[0018] (3) increasing the final height;

[0019] The mechanism of promoting the height development comprises any one or several of the following:

[0020] 1) activating the growth axis;

[0021] 2) promoting bone formation; and / or,

[0022] 3) promote bone absorption of minerals.

[0023] Possibly, the subject is a mammal, preferably a human.

[0024] Possibly, the composition is a pharmaceutical composition, or a food composition and / or a health product composition for non-therapeutic purposes.

[0025] In a second aspect, the present application provides a composition for promoting height development of a minor subject, the composition comprising: a Faecalibacterium prausnitzii YG0564 and a human milk oligosaccharide.

[0026] As a preference, the human milk oligosaccharide is selected from the group consisting of 2'-fucosyllactose, lacto-N-neotetraose, 3'-sialyllactose, lacto-N-tetraose and 6'-sialyllactose, further preferably 2'-fucosyllactose and / or lacto-N-neotetraose, more preferably 2'-fucosyllactose;

[0027] As a preference, the ratio of the Faecalibacterium prausnitzii YG0564 and the human milk oligosaccharide is (10 8 -10 10 ) CFU: (20-500) mg, further preferably (5 x 10 8 -5 x 10 9 ) CFU: (50-200) mg, most preferably 10 9 CFU: 100 mg.

[0028] In a possible embodiment, the composition is a pharmaceutical composition, or a food composition and / or a health product composition for non-therapeutic purposes.

[0029] In a third aspect, the present application provides a method for promoting height development of a minor subject, the method comprising: administering to a subject in need thereof an effective amount of a Faecalibacterium prausnitzii YG0564 or a composition as described in the above-mentioned second aspect.

[0030] Beneficial effects

[0031] The present application first discovers that the Faecalibacterium prausnitzii YG0564 exhibits unique advantages in promoting height development of a minor subject, especially under a malnourished dietary pattern, and its effect of promoting height development of a minor subject is more significant compared to traditional lactobacilli and bifidobacteria. In the prior art, the research on the growth-promoting effect of animal bifidobacterium BL-11 is mostly limited to normal dietary patterns, while the present application discovers the excellent performance of the Faecalibacterium prausnitzii YG0564 under the special dietary pattern of malnutrition, which makes up for the deficiencies of traditional strains in this respect.

[0032] The present application first proposes that the multiple fusicatenaria YG0564 is combined with HMO to promote the height development of the underage subjects; experiments prove that the two have significant synergistic effect on promoting the height development of children. Although there are compositions of HMO and other components in the prior art, they mainly focus on other health indicators, and the synergistic effect of the present application on the height development of children is not clear. The present application provides a new and efficient combination scheme for the height development of children.

[0033] In addition, the present application also fills the research gap of special dietary patterns. The present application focuses on the height development problem of children under malnutrition dietary pattern, and develops targetedly. Unlike the existing probiotic technology which mainly focuses on the growth and development of children under normal dietary pattern, the present application effectively solves the problem of lack of effective probiotic solution for the height development of children under malnutrition pattern, and provides strong support for improving the height development of children under special dietary pattern. BRIEF DESCRIPTION OF DRAWINGS

[0034] One or more embodiments are illustrated by way of example in the figures that constitute a part of this patent document. The illustrative examples set forth in the figures are not to be construed as limiting the embodiments. The word "exemplary" is used herein to mean "serving as an example, instance, or illustration." Any implementation described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other implementations.

[0035] Figure 1 It is shown that multiple fusicatenaria YG0564 significantly improves the growth retardation of malnourished mice; wherein, A is a body length growth rate curve, and B shows the net growth value of the terminal body length; wherein, * represents: compared with the malnutrition model control group (i.e. MAL group), p<0.05.

[0036] Figure 2 It is shown that multiple fusicatenaria YG0564 combined with 2'FL can significantly promote the physical growth of mice; wherein, A is a body length growth rate curve, B shows the net growth value of the terminal body length, C is a photo of the mouse body, D is a photo of the mouse femur and tibia, E is the tibia bone length of the mouse, and F is the femur bone length of the mouse; wherein, * represents: compared with the MAL group, p<0.05, ** represents: compared with the MAL group, p<0.01, and ns represents: compared with the MAL group, no significant difference.

[0037] Figure 3 It is shown that the relative activity (%) of multiple fusicatenaria YG0564 in different HMO culture media; wherein, # represents: compared with the Glc group, p<0.05, ## represents: compared with the Glc group, p<0.01, and ### represents: compared with the Glc group, p<0.001.

[0038] Figure 4The combination of Moraxella fowl YG0564 and 2'FL can activate the GH / IGF growth axis of mice; Figure A shows the serum GH level of mice, Figure B shows the serum IGF-1 level of mice, Figure C shows the IGF-1 level of liver tissue homogenate of mice, Figure D shows the serum bone formation marker PINP level, Figure E shows the blood phosphorus level of mice, and Figure F shows the blood calcium level of mice; * represents p<0.05 compared with the MAL group, ** represents p<0.01 compared with the MAL group, and *** represents p<0.001 compared with the MAL group. DETAILED DESCRIPTION

[0039] In order to make the objects, technical solutions, and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are some but not all of the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the scope of the present application. Unless otherwise clearly indicated, in the entire specification and claims, the term “comprise” or its variants such as “contain” or “include” should be understood as including the stated elements or components, and not excluding other elements or components.

[0040] In addition, in order to better illustrate the present application, numerous specific details are given in the specific embodiments below. Those skilled in the art should understand that the present application can also be implemented without some specific details. In some embodiments, the raw materials, elements, methods, means, and the like that are well known to those skilled in the art are not described in detail, so as to highlight the main idea of the present application.

[0041] In the following examples, unless otherwise specified, the reagents or raw materials used are commercially available.

[0042] In the following examples, the formula of the normal feed and the low-protein low-fat feed used is shown in Table 1 below.

[0043] Table 1, formula of normal feed and low-protein low-fat feed

[0044]

[0045]

[0046] Example 1: Moraxella fowl YG0564 can promote the height development of suckling mice

[0047] The inventors had previously successfully isolated some probiotics from healthy human samples. In this embodiment, six of these probiotic strains (including four traditional probiotics (Lactobacillus paracasei YGMCC2360, Bifidobacterium animalis YGMCC00002, Bifidobacterium longum YGMCC0979, and Bifidobacterium breve YGMCC2418) and two novel strains (Ackermania myxophilus YGMCC2645 and Fossia dorsalis YG0564, both of which are deposited at the China General Microbiological Culture Collection Center, with accession numbers CGMCC No. 30598 and CGMCC No. 27578, respectively) were used to construct a malnourished suckling mouse model to test the effects of these probiotics on the height development of malnourished suckling mice.

[0048] Specifically, 56 weaned male C57BL / 6J mice (21 days old, purchased from Vital Rivers) were used. The mice were acclimatized to a normal diet for 2 days, and then randomly divided into 8 groups of 7 mice each. The normal control group (i.e., the "Con" group in the figure) was fed a normal diet, drank sterile water, and received 100 μL of PBS by gavage daily. The malnutrition model control group (i.e., the "MAL" group in the figure) was fed a low-protein, low-fat diet, drank sterile water, and received 100 μL of PBS by gavage daily. The bacterial strain treatment groups were fed a low-protein, low-fat diet and each mouse was orally administered 1*10^9 CFU of live bacteria (resuspended in 100 μL of PBS) daily for 5 weeks. Feed consumption was recorded weekly, and body weight and length were measured weekly. Mice were briefly anesthetized with isoflurane for length measurement.

[0049] The results are as follows Figure 1 As shown. Figure 1 Figure A shows the growth rate curve of body length of suckling mice in each strain treatment group, and Figure B shows the final net growth value of body length of suckling mice in each strain treatment group.

[0050] Depend on Figure 1 As shown in Figure A, all probiotics showed varying degrees of growth-promoting effects in the early stage of intervention (week 1). Notably, after 1 week of intervention, *Focusia dorsalis* YG0564 showed a sustained growth-promoting advantage: the body length change rate remained at a high level, eventually reaching a cumulative change rate of 115.8%, which was significantly higher than the 112.3% of the malnutrition model control group.

[0051] Depend on Figure 1 As shown in Figure B, in terms of the final net increase in body length, the *Focusia dorsalis* YG0564 group ultimately achieved a net increase of 11.67 mm, which is about 30% higher than the malnutrition model control group (8.98 mm), and significantly better than other traditional probiotics and the novel control probiotic *Ackermania muscaria* YGMCC2645.

[0052] This study first confirmed that the unique advantage of the Forsythia plurimacida YG0564 in improving malnutrition-related growth retardation. Compared with 4 traditional probiotics (Lactobacillus paracasei / Bifidobacterium animalis / Bifidobacterium longum / Bifidobacterium breve) and a new control strain Akkermansia muciniphila, the Forsythia plurimacida YG0564 showed two core advantages: ①Sustained growth-promoting effect: maintained stable growth-promoting activity in 5 weeks of intervention, while the effect of traditional probiotics significantly decreased with the extension of intervention time (for example, Akkermansia muciniphila YGMCC2645 and Bifidobacterium longum YGMCC0979) or always played a weak effect (for example, Lactobacillus paracasei YGMCC2360 and Bifidobacterium animalis YGMCC00002), ②Significant growth gain: the change rate of body length at the end (115.8% vs. the average of traditional bacteria group 113.1%) and the net growth (11.67 mm vs. the average of traditional bacteria group 9.60 mm) reached statistically significant difference (p<0.05), and the growth-promoting efficiency was increased by 21.56% compared with traditional probiotics.

[0053] This finding suggests that the Forsythia plurimacida YG0564 may achieve long-term growth regulation through a mechanism different from traditional probiotics, providing a more potential candidate strain for clinical nutritional intervention.

[0054] Example 2: Synergistic effect of Forsythia plurimacida YG0564 combined with HMOs in promoting the growth of children's height

[0055] In this example, the ability of Forsythia plurimacida YG0564 combined with HMOs to promote the growth of rat height was explored. In this study, we explored the synergistic effect of Forsythia plurimacida YG0564 combined with 2'FL (2'-fucosyllactose) in promoting the growth of malnourished rat height.

[0056] The method for constructing a malnourished rat model is described in Example 1. For comparative analysis, the experiment was divided into the following groups:

[0057] (1) Normal control group (i.e., "Con" group in the figure): normal feed, drink sterilized water, 100 μL PBS gavage every day;

[0058] (2) Model control group (i.e., "MAL" group in the figure): low-protein low-fat feed, drink sterilized water, 100 μL PBS gavage every day;

[0059] (3) 2'FL alone intervention group (i.e., "2'FL" group in the figure): low-protein low-fat feed, drink sterilized water, 2'FL dosage of 5 mg / g body weight, dissolved in 100 μL PBS gavage;

[0060] (4) YG0564 alone intervention group (i.e., "0564" group in the figure): low-protein low-fat feed, drink sterilized water, YG0564 live bacteria administration amount is 5*10^7 CFU / g body weight, dissolved in 100 μL PBS gavage;

[0061] (5) YG0564 combined with 2'FL intervention group (i.e., "2'FL+0564" group in the figure): low-protein low-fat feed, drink sterilized water, according to 2'FL 5mg / g body weight and YG0564 live bacteria 5*10^7 CFU / g body weight administration amount, the required amount of 2'FL and YG0564 live bacteria are resuspended in 100 μL PBS mixed gavage.

[0062] The results are shown in Figure 2 . Figure 2 Among them, A is the body length growth rate curve, B shows the terminal body length net growth value, C is the mouse size photo, D is the mouse femur and tibia photo, E is the mouse tibia bone length, and F is the mouse femur bone length.

[0063] It can be seen from Figure 2 that:

[0064] (1) Malnourished model control group (i.e., MAL group): after 5 weeks of long-term modeling, the growth of the MAL group of suckling mice was significantly impaired (as shown in A-C of Figure 2 ), the size growth was slow, the growth rate was only 112.2%, and the net growth was 9.74mm. In addition, the length of femur and tibia was significantly shortened (as shown in D-F of Figure 2 );

[0065] (2) 2'FL alone intervention group: this group did not show significant growth-promoting effect, and the body length and bone length were not significantly improved compared with the MAL group;

[0066] (3) YG0564 alone intervention group: the growth rate of the suckling mice in this group reached 114.0%, and the net body length growth was about 1.5mm more than that of the MAL group (p<0.05), which showed that the probiotic bacteria could partially reverse the growth retardation phenomenon caused by malnutrition; the bone length of femur and tibia also increased slightly;

[0067] (4) YG0564 combined with 2'FL intervention group: the growth of the suckling mice in this group was the fastest, and the growth-promoting effect was the most significant, with a growth rate of 115.88% (as shown in A of Figure 2 ), a net body length growth of 12.43mm (as shown in B of Figure 2 ), and a significant increase in bone length, especially the tibia (about 0.3mm longer, p<0.05).

[0068] The above results suggest that although 2'FL alone does not significantly promote growth, when combined with YG0564, it can significantly enhance the growth-promoting effect. It is speculated that this may be related to the enhanced activity of the HMO metabolic pathway (GH29 / GH95) of YG0564, and the role of 2'FL as a metabolic substrate may improve the growth-promoting function of YG0564.

[0069] Through these experiments, we reveal the potential synergistic effect of YG0564 and 2'FL in nutritional supplementation of suckling mice, and this combination may be an effective strategy to address growth retardation caused by malnutrition.

[0070] Example 3: In vitro HMO utilization effect of B. dorei YG0564

[0071] To explore the potential mechanism of the synergistic effect of B. dorei YG0564 combined with human milk oligosaccharides (HMOs), we analyzed the HMO metabolism-related gene profiles of B. dorei YG0564 and some traditional probiotics and other new probiotics through the CAZy database system, and focused on the distribution characteristics of two key hydrolytic enzymes, fucosidase (GH29, GH95) and sialidase (GH33). The results are shown in Table 2.

[0072] Table 2. Analysis of HMO utilization gene clusters in different probiotic genomes

[0073]

[0074] As can be seen from Table 1, there are significant differences compared with traditional probiotics: (1) Traditional probiotic deficiencies: The reference strains including B. animalis subsp. lactis BB-12, L. rhamnosus GG and L. plantarum ATCC 14917 all have key enzyme deletions, and only some strains retain a single type of enzyme; (2) New probiotic dominance: B. dorei YGMCC0564 (i.e., B. dorei YG0564) and A. muciniphila YGMCC2645 exhibit a complete HMO hydrolytic enzyme system, and the copy numbers of GH29, GH95 and GH33 genes of YGMCC0564 are 9, 7 and 4 respectively, which are significantly higher than those of A. muciniphila. This genomic characteristic indicates that B. dorei YGMCC0564 has a unique molecular basis for efficient metabolism of HMOs, which may be one of the mechanisms of its synergistic effect with HMOs.

[0075] To verify the HMO metabolic ability of the Forsythia plurimaculata YG0564, we evaluated its growth performance in different HMOs as the sole carbon source by spectrophotometry; and quantitatively characterized its HMO utilization efficiency by calculating the OD600 ratio of the strain in HMO medium to that in glucose medium (growth vigor index = [HMO medium OD600 / glucose medium OD600] x 100%), and the results are shown in Table 1. Figure 3 .

[0076] Figure 3 The experimental results revealed two key findings: (1) broad-spectrum metabolic advantage: the utilization ability of the Forsythia plurimaculata YG0564 to all the tested HMOs (2'-fucosyllactose [2'FL], lacto-N-neotetraose [LNnT], 3'-sialyllactose [3'SL], lacto-N-tetraose [LNT], 6'-sialyllactose [6'SL]) was significantly higher than that of the glucose control group (p < 0.01); (2) substrate preference: the metabolic efficiency of the Forsythia plurimaculata YG0564 to 2'FL and LNnT reached 256.8% and 242.3% of the glucose control, which was significantly better than that to other HMOs (3'SL: 179.5%, LNT: 166.4%, 6'SL: 159.3%). This data is highly consistent with the previous genomic analysis (high copy number of GH29 / GH95), indicating that the Forsythia plurimaculata YG0564 has the biological characteristics of directed degradation of fucosylated HMOs.

[0077] Example 4: Forsythia plurimaculata YG0564 and Forsythia plurimaculata YG0564 combined with 2'FL can activate the GH / IGF growth axis and promote bone formation and mineral absorption

[0078] To explore the mechanism of the Forsythia plurimaculata YG0564 and the Forsythia plurimaculata YG0564 combined with 2'FL in promoting the height development of malnourished mice, this embodiment explores their effects on the GH / IGF growth axis, bone formation, and mineral absorption.

[0079] Specifically, the experiments were carried out according to the following grouping:

[0080] (1) normal control group (i.e., "Con" group in the figure): normal feed, sterilized water for drinking, 100 μL PBS for gavage every day;

[0081] (2) malnutrition model control group (i.e., "MAL" group in the figure): low-protein low-fat feed, sterilized water for drinking, 100 μL PBS for gavage every day;

[0082] (3) 2'FL alone intervention group (i.e., "2'FL" group in the figure): low-protein low-fat feed, sterilized water for drinking, 2'-FL was administered at a dose of 5 mg / g body weight, dissolved in 100 μL PBS for gavage;

[0083] (4) YG0564 alone intervention group (i.e., the "0564" group in the figure): low-protein low-fat feed, drinking sterilized water, YG0564 live bacteria administration amount is 5*10^7 CFU / g body weight, dissolved in 100 μL PBS gavage;

[0084] (5) YG0564 combined with 2'FL intervention group (i.e., the "2'FL+0564" group in the figure): low-protein low-fat feed, drinking sterilized water, 2'-FL 5 mg / g body weight and YG0564 live bacteria 5*10^7 CFU / g body weight administration amount, the required amount of 2'FL and YG0564 live bacteria are resuspended in 100 μL PBS mixed gavage.

[0085] At the end of each group experiment, the mice were euthanized, blood was collected for serological detection, and liver tissue was collected for GH / IGF-1 growth axis related factor detection.

[0086] Growth hormone (GH) plays an extremely important role in human growth and development. It promotes longitudinal bone growth by stimulating chondrocyte proliferation and differentiation in the bone growth plate, thereby increasing height. In children and adolescents, insufficient GH secretion can lead to growth retardation or even dwarfism. Therefore, we first detected GH in the serum of each group of mice, and the results are shown in Figure 4 A of the figure, which shows that the GH level of the malnourished MAL mice is indeed decreased, while the GH levels of the three experimental groups are increased to varying degrees, from low to high, in order of 2'FL group, YG0564 group and the combined use of the two groups. Therefore, strain YG0564, 2'FL and their combination can promote the secretion of mouse GH, showing a positive effect. In particular, the GH level of the combined use group is about twice that of the model group, significantly better than either of the single intervention groups.

[0087] In the GH pathway, IGF-1 (insulin-like growth factor 1) is an essential link. GH mainly stimulates the liver to produce IGF-1, which in turn promotes longitudinal bone growth. Next, we detected the IGF-1 levels in the liver and serum of each group of mice. The results are shown in Figure 4Figure 6 shows the serum IGF-1 levels and liver IGF-1 levels of the mice in the experiment. As shown in the B-C graphs of Figure 6, it is shown that: 1) the serum IGF-1 levels and liver IGF-1 levels of the malnourished MAL mice are significantly lower than those of the normal mice; 2) for the serum IGF-1 levels, the serum IGF-1 levels of the YG0564 group and the YG0564 combined with 2'FL group are significantly higher than those of the model control group; 3) for the liver IGF-1 levels, only the liver IGF-1 levels of the YG0564 combined with 2'FL group are significantly higher than those of the model control; 4) 2'FL alone cannot restore the serum or liver IGF-1 levels. Thus, it is proved that only the intervention of YG0564 can precisely activate the GH / IGF-1 growth axis, and 2'FL can only assist to strengthen this effect.

[0088] PINP (I-type procollagen amino-terminal propeptide) is one of the markers of bone formation, which reflects the synthesis of bone collagen and the process of bone formation. During growth and development, bone formation and remodeling are constantly ongoing, and the level of PINP can reflect the degree of active bone growth. Therefore, we also detected the PINP levels in the serum of the mice in each group, and the detection results are shown in Figure 4 Figure 6D shows that compared with the model group, the bone formation of the three experimental groups is increased to different degrees, and the YG0564 intervention group and the YG0564 combined with 2'FL intervention group are significantly different from the model control group, which shows that YG0564 and 2'FL can both promote bone formation and increase the degree of active bone growth, and the two substances have a synergistic effect.

[0089] Blood calcium and blood phosphorus are important components of bone mineralization. During growth and development, the growth and mineralization of the skeleton require sufficient supply of blood calcium and blood phosphorus. Next, we detected the blood phosphorus levels and blood calcium levels of the mice in each group, and the results are shown in Figure 4 Figures 6E and 6F show that YG0564 and 2'FL can both help restore blood phosphorus, but have no effect on blood calcium; after being combined, the blood calcium and blood phosphorus are significantly increased, which shows that they have a close synergistic effect in promoting mineral absorption and utilization, especially calcium ions.

[0090] In summary, the intervention of strain YG0564 can activate the GH / IGF-1 growth axis of mice, promote the proliferation and differentiation of bone cells, promote the absorption and utilization of minerals, increase bone formation, and thus promote the longitudinal growth of the skeleton; and the combined use of HMOs can synergistically promote this effect and further rescue the developmental retardation caused by malnutrition. The strategy of using YG0564 and HMOs in combination provides a better solution for the growth and development of children and adolescents with malnutrition (or insufficient nutrient intake).

[0091] It should be pointed out finally that the above embodiments are only used to illustrate the technical solutions of the present application, but not to limit the same; and although the present application has been described in detail with reference to the foregoing embodiments, it should be appreciated by those skilled in the art that the technical solutions recorded in the foregoing embodiments can be modified, or some technical features thereof can be replaced equivalently; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. The use of *Focusella dorsalis* YG0564 in the preparation of compositions for promoting height development in underage subjects, characterized in that, Phocaeicola dorei YG0564 is deposited at the China General Microbiological Culture Collection Center (CGMCC), with the classification name Phocaeicola dorei, deposit date of June 7, 2023, and accession number CGMCC No. 27578.

2. The use according to claim 1, characterized in that, The minor subjects were malnourished minor subjects.

3. The use according to claim 1 or 2, characterized in that, In the composition, *Focusia dorsalis* YG0564 is either the sole active ingredient or one of the active ingredients.

4. The use according to claim 3, characterized in that, The active ingredient of the composition also includes human milk oligosaccharides; Preferably, the human milk oligosaccharide is selected from: 2'-fucosylated lactose, lactose-N-neotetrasaccharide, 3'-sialylated lactose, lactose-N-tetrasaccharide and 6'-sialylated lactose, more preferably 2'-fucosylated lactose and / or lactose-N-neotetrasaccharide, and most preferably 2'-fucosylated lactose; Preferably, the ratio of *Focusia dorsalis* YG0564 to human milk oligosaccharides is (10:10). 8 -10 10 CFU: (20-500) mg, more preferably (5×10⁻⁶) mg. 8 -5×10 9 CFU: (50-200) mg, optimally 10 mg 9 CFU: 100mg.

5. The use according to any one of claims 1-4, characterized in that, The promotion of height development includes: (1) Improve malnutrition-related growth retardation; (2) Promotes height growth; and / or, (3) Increase the height at the finish line; And / or, the mechanisms promoting height development include any one or more of the following: 1) Activate the growth axis; 2) Promotes bone formation; and / or, 3) Promotes the absorption of minerals by bones.

6. The use according to any one of claims 1-5, characterized in that, The subjects are mammals, preferably humans.

7. The use according to any one of claims 1-6, characterized in that, The composition is a pharmaceutical composition, or a food composition and / or health product composition for non-therapeutic purposes.

8. A composition for promoting height development in underage subjects, characterized in that, The composition comprises: Fauciella dorsalis YG0564 and human milk oligosaccharides.

9. The composition according to claim 8, characterized in that, The human milk oligosaccharide is selected from: 2'-fucosylated lactose, lactose-N-neotetrasaccharide, 3'-sialylated lactose, lactose-N-tetrasaccharide and 6'-sialylated lactose, preferably 2'-fucosylated lactose and / or lactose-N-neotetrasaccharide, more preferably 2'-fucosylated lactose; And / or, the ratio of *Focusia dorsalis* YG0564 to human milk oligosaccharides is (10:10). 8 -10 10 CFU: (20-500) mg, more preferably (5×10⁻⁶) mg. 8 -5×10 9 CFU: (50-200) mg, optimally 10 mg 9 CFU: 100mg.

10. The composition according to claim 8 or 9, characterized in that, The composition is a pharmaceutical composition, or a food composition and / or health product composition for non-therapeutic purposes.

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