February 20, 2019

Alison Lawton
Chief Executive Officer
Kaleido Biosciences, Inc.
65 Hayden Avenue
Lexington, MA 02421

       Re: Kaleido Biosciences, Inc.
           Amendment No. 1 to Registration Statement on Form S-1
           Filed February 19, 2019
           File No. 333-229204

Dear Ms. Lawton:

      We have reviewed your amended registration statement and have the
comments. In some of our comments, we may ask you to provide us with
information so we
may better understand your disclosure.

       Please respond to this letter by amending your registration statement
and providing the
requested information. If you do not believe our comments apply to your facts
circumstances or do not believe an amendment is appropriate, please tell us why
in your

       After reviewing any amendment to your registration statement and the
information you
provide in response to these comments, we may have additional comments. Unless
we note
otherwise, our references to prior comments are to comments in our November 27,
2018 letter.

Amendment No. 1 to Registration Statement on Form S-1 filed February 19, 2019

Use of Proceeds, page 84

1.     We note that you have not addressed our prior comment 15 in our letter
dated October 23,
       2018. Please revise your disclosure to specify whether you will be able
to complete the
       Phase 2 clinical trials for your hyperammonemia programs and whether
this covers
       completion of Phase 2 trials for both UCD and HE. Please also disclose
how far in the
       development of your other pipeline product candidates you expect to
reach using proceeds
       from the offering. If any material amounts of other funds are necessary
to accomplish the
       specified purposes for which the proceeds are to be obtained, state the
amounts and
       sources of such other funds needed for each such specified purpose and
the sources
       thereof. Refer to Instruction 3 to Item 504 of Regulation S-K.
 Alison Lawton
Kaleido Biosciences, Inc.
February 20, 2019
Page 2
Future plans for clinical development in UCD, page 130

2.     We note your disclosure that UCD primarily affects pediatric patients.
We further note
       that your planned Phase 2 clinical trial will enroll only adults but is
intended to allow for
       you to evaluate the efficacy of KB195 in reducing ammonia in UCD
patients so that you
       can support the inclusion of pediatric patients as soon as possible.
Please clearly state
       why you cannot include pediatric patients in your Phase 2 clinical trial
and what
       specifically you must demonstrate in the trial in order to support the
inclusion of pediatric
       patients. Please also clearly state in your summary and elsewhere that
you discuss the
       Phase 2 trial that UCD is primarily a pediatric disease but you only
have approval for
       clinical testing of adults. Please state the potential impact or adverse
effects if you are
       unable to extend clinical testing to pediatric patients. Please also
include relevant risk
       factor disclosure.
Future pipeline opportunities, page 138

3.     We note your statement on page 139 that the MMT you evaluated in your
non-IND human
       clinical study demonstrated favorable safety and tolerability. Findings
of safety and
       efficacy are determinations that are solely within the authority of the
FDA. Please delete
       this statement.
Description of Capital Stock
Choice of forum, page 198

4.     We note your disclosure on page 80 that if the Court of Chancery of the
State of Delaware
       does not have jurisdiction, the federal district court for the District
of Delaware or other
       state courts of the State of Delaware shall be the exclusive forum for
certain state law
       claims. However, we note that these alternative forums are not listed in
your Amended
       and Restated By-Laws or in your disclosure on page 198. Please revise
your disclosure
       and/or your Amended and Restated By-Laws to reconcile this discrepancy.
       You may contact Keira Nakada at 202-551-3659 or Jim Rosenberg at
202-551-3679 if
you have questions regarding comments on the financial statements and related
matters. Please
contact Irene Paik at 202-551-6553 or Erin Jaskot at 202-551-3442 with any
other questions.

FirstName LastNameAlison Lawton
                                                              Division of
Corporation Finance
Comapany NameKaleido Biosciences, Inc.
                                                              Office of
Healthcare & Insurance
February 20, 2019 Page 2
cc:       Kingsley L. Taft - Goodwin Procter LLP
FirstName LastName