Multi-Omics Analysis Reveals Age-Related Microbial and Metabolite Alterations in Non-Human Primates

Round 1

Reviewer 1 Report

The reviewer highly appreciates the authors' multi-omics analysis to investigate the age-related microbial and metabolite alterations in non-human primates. However, there are few comments which the authors need to address; 

1.  Age stratification: The reviewer checked the references provide by the authors on age stratification (Li et al 2019 and Janiak et al 2021) for this study. Hence, the inclusion of 16yr rhesus macaques in old age category need to be addressed. In both the references, the author mentioned aged or old adults instead of adults for above 15 yr. 

Also, the reviewer would like to recommend authors to read the published article titled; "An overview of nonhuman primates in aging research" by Juile et al (DOI:10.1016/j.exger.2016.12.005)

" In general, rhesus monkeys aged 15–22 years are deemed middle aged, while those over 30 years are considered old or elderly" 

2. The reviewer would suggest the author to mention a sentence or a paragraph in introduction section regarding 16s rRNA. 

Author Response

For research article

1. Li, M.L.; Wu, S.H.; Zhang, J.J.; Tian, H.Y.; Shao, Y.; Wang, Z.B.; Irwin, D.M.; Li, J.L.; Hu, X.T.; Wu, D.D. 547 transcriptomes from 44 brain areas reveal features of the aging brain in non-human primates. Genome biology 2019, 20, 258, doi:10.1186/s13059-019-1866-1.
2. Rhoades, N.S.; Davies, M.; Lewis, S.A.; Cinco, I.R.; Kohama, S.G.; Bermudez, L.E.; Winthrop, K.L.; Fuss, C.; Mattison, J.A.; Spindel, E.R.; et al. Functional, transcriptional, and microbial shifts associated with healthy pulmonary aging in rhesus macaques. Cell reports 2022, 39, 110725, doi:10.1016/j.celrep.2022.110725.
3. Beckman, D.; Ott, S.; Donis-Cox, K.; Janssen, W.G.; Bliss-Moreau, E.; Rudebeck, P.H.; Baxter, M.G.; Morrison, J.H. Oligomeric Aβ in the monkey brain impacts synaptic integrity and induces accelerated cortical aging. Proceedings of the National Academy of Sciences of the United States of America 2019, 116, 26239-26246, doi:10.1073/pnas.1902301116.
4. Thomé, A.; Gray, D.T.; Erickson, C.A.; Lipa, P.; Barnes, C.A. Memory impairment in aged primates is associated with region-specific network dysfunction. Molecular psychiatry 2016, 21, 1257-1262, doi:10.1038/mp.2015.160.
5. Keuker, J.I.; Luiten, P.G.; Fuchs, E. Capillary changes in hippocampal CA1 and CA3 areas of the aging rhesus monkey. Acta neuropathologica 2000, 100, 665-672, doi:10.1007/s004010000227.
6. Duan, J.; Yin, B.; Li, W.; Chai, T.; Liang, W.; Huang, Y.; Tan, X.; Zheng, P.; Wu, J.; Li, Y.; et al. Age-related changes in microbial composition and function in cynomolgus macaques. Aging 2019, 11, 12080-12096, doi:10.18632/aging.102541.
7. Tan, X.; Chai, T.; Duan, J.; Wu, J.; Zhang, H.; Li, Y.; Huang, Y.; Hu, X.; Zheng, P.; Song, J.; et al. Dynamic changes occur in the DNA gut virome of female cynomolgus macaques during aging. MicrobiologyOpen 2021, 10, e1186, doi:10.1002/mbo3.1186.
8. Langille, M.G.; Zaneveld, J.; Caporaso, J.G.; McDonald, D.; Knights, D.; Reyes, J.A.; Clemente, J.C.; Burkepile, D.E.; Vega Thurber, R.L.; Knight, R.; et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nature biotechnology 2013, 31, 814-821, doi:10.1038/nbt.2676.

Reviewer 2 Report

In the manuscript submitted to me for review entitled " Multi-omics reveals age-related microbial and metabolite alterations in non-human primates“ the authors Xiang Chen, Yiyun Liu, Juncai Pu, Siwen Gui, Dongfang Wang, Xiaogang Zhong, Wei Tao, Xiaopeng Chen, Weiyi Chen, Yue Chen, Renjie Qiao and Peng Xie present their research on age-related changes in the gut, serum and fecal metabolome in male rhesus macaques.

The research is extremely important because it helps to track some of the changes occurring in the body during the aging process. Such research would contribute to the control of these changes to control some of the symptoms accompanying the aging process and possibly increase life expectancy.

The methods used are correctly selected and described. The obtained results correspond to the conclusions drawn by the authors. The authors present their results in 5 figures, 6 supplementary figures and 1 supplementary table.

In support of their research, the authors presented 83 references, most of which are from the last 20 years, but there are also studies from 4 decades ago. Of all the references, 51 are from the last 5 years (nearly 2/3 of the total number), of which 5 are from 2023.

I congratulate the authors for the chosen topic and the scale of the research conducted. I have no objections to the conduct of the experiments themselves and their description. I have only a few recommendations that, if I were a reader of the article, I would have preferred to have been included in the manuscript by the authors.

1. The font in figures 1, 2, 3 and 4 is too small and illegible. It frustrates the reader. If possible, the authors could increase the font or the size of the figures themselves.

2. 6 supplementary figures and 1 table are presented in a separate file. A link to them is provided. But I personally am a reader who, when reading about some results, prefers to see them rather than looking for them somewhere else. I believe that the information in the supplementary figures is important to the results obtained, and my personal opinion is that at least some of the figures should be included in the main part of the manuscript.

3. Some of the references do not list all authors. I think it is more representative and complete when all authors are listed. These are reference numbers: 6, 9, 10, 12, 14, 17, 19, 21, 23, 25, 26, 30, 32, 33, 38, 39, 55, 57, 59, 64, 65, 73 and 79. Let all the authors be added.

Author Response

For research article